It’s a normal day in the city and Doctor Singh is working hard at the hospital. There are more patients than usual, and at first it looks just like a normal cough. However soon the patients get worse and no cure is found.
The news announce that a virus called H5G9 or “the Sick” has been discovered and classified as the deadliest in history. When Singh goes home, he’s devastated to discover his wife Rani is infected too. He immediately puts her in his car and rushes to the hospital, which is harder than it sounds because people are panicking on the streets, causing lots of riots and violence.
Later at the hospital the nurses call Singh to check on the latest newborn babies and he’s shocked to discover they were all born with animal parts. They are classified as “hybrids” but scientists don’t know if they brought the virus or they’re a consequence of it, so people fear them. At the same time, Richard runs with a deer baby to hide at the Yellowstone National Park.
He renovates an abandoned house and puts up a fence so they can live in peace. The virus ends up wiping out most of humanity and society collapses - this event is known as “The Great Crumble”. In the forest, Richard raises Gus, who grows up calling his dad “pubba”.
Richard makes toys and books for him, but he never tells him about the outside world, doesn’t let him cross the fence, and teaches him to hide if he ever sees another human. Whenever a plane flies by, Richard covers Gus’ ears. One day a plane drops some flyers about a refuge for hybrids, and Richard burns them all before Gus can see them.
When Gus turns seven, Richard finally tells him about The Great Crumble and how people hate hybrids. He also says Gus’ mother is dead but doesn’t add any details. That night Richard buries a box of mementos from his old life.
Sometime later, Gus dares to cross the fence to follow some footprints and hears a scary growl. Richard soon finds him and drags him back, scolding him for his actions. Gus is sure a deer is his mother, but Richard denies it and Gus runs into the house to cry.
At that moment they hear a voice in the distance and Richard immediately grabs his gun. The other man explains he’s looking for his missing sister. Richard tells him no woman came by and asks about the world, so the man explains the Sick has slowed down but it’s still out there.
Suddenly Gus moves among the plants and Richard checks on him. When he looks up again the man is gone but he left ribbons tied to the fence. Realizing they’ve been marked, Richard makes Gus hide in a secret compartment in the house and grabs a special injection before heading out.
Gus waits for a while and is startled by a noise, but it’s just a deer. He tries touching it, however the animal runs away when it hears yelling nearby. Then Richard comes back and tell Gus “he won’t hurt you now” before collapsing.
Gus immediately takes him to bed. The next morning Richard tells Gus that his mother was called Birdie and she would be proud of him. Unfortunately a few hours later, Richard passes away on his chair.
Weeks pass and Gus does his best to survive alone while keeping straw dolls for company. One day he gets too frustrated with the garden and throws a lamp at the weeds, which accidentally starts a fire. He puts it out by throwing things at it, like his precious dog plush.
Afterward he finds an old map he drew years ago and starts following it until he finds a tree with a heart and an arrow. He starts digging on that spot and finds Richard’s box, which contains money, credit cards, IDs, a photo of his mother Birdie, and a poster for the hybrid refuge. The picture says “Colorado”, so Gus checks the map and decides to go there to find his mother.
After packing up his stuff, he makes it to the fence and finds some candy bars on the ground. He loves the taste of the first one and tries to grab another one, but it’s pulled away by thread. Suddenly an arrow flies out and Gus runs to hide, noticing there’s a hunter nearby.
He gets ready to hit him with his slingshot but a second hunter appears behind him and grabs him. The hunters say that Gus is bigger than other hybrids and call him special, so they want to take him to a lab. Gus manages to hit the guy and frees himself as he yells, causing the men to be surprised he can talk.
When the hunters get ready to kill him, they get show down first. Tommy appears and kills the hunters while Gus runs away. He hides in his home, but soon Tommy finds him and takes him out of his hiding spot, explaining he found him because of the smoke.
Tommy is also shocked to hear Gus can talk and sees Birdie’s picture. Then he warns Gus that some people hunt hybrids to sell their animal parts while fixing his broken pipes. Tommy also gives him a few tips on how to take care of the farm and calls Gus “sweet tooth” before leaving.
Ignoring all the warnings, Gus runs after Tommy and asks him to take him to Colorado. A flashback shows Aimee working as a therapist and hating the routine. When the virus outbreak happens, she’s forced to stay in her office.
Weeks pass and the lockdown becomes too much so Aimee finally goes outside, only to discover the elephants have escaped from the zoo. Aimee runs to the zoo and frees the birds from their cages too. She starts living there and for years she’s alone but happy, until one day she discovers a hybrid baby abandoned in a box.
In the present, Gus continues to follow Tommy around, ignoring his protests. At night, Gus’ eyes become really creepy but Tommy agrees to share some of his food anyway. The next morning, Tommy discovers Gus ate all his provisions and gets furious, so Gus apologizes by explaining he can find food with his enhanced sense of smell.
They come across an abandoned visitor center and Gus goes inside, but he gets terrified when he sees a deer head on the wall. When he tries to run away, he steps on a trap and is caught by a net. It turns out a family leaves there and when they see Gus isn’t a hunter, they invite him and Tommy to have lunch with them.
The family keeps wearing their masks, so Tommy assures them he isn’t infected and that hybrids like Gus can’t carry the virus at all. For the first time, Gus gets to play with another kid and real toys, he also discovers he shakes his leg if someone scratches him behind the ears and hears music for the first time. The family father recognizes Tommy as a football star, but Tommy doesn’t want to talk about it.
In the forest, the Last Men appear. They’re a paramilitary group who kill hybrids, and now they’ve found Tommy’s trash. Meanwhile in a town in Gideon, Singh notices that Rani’s pinky is shaking, which is a sign that the Sick is coming back.
He immediately gives her an injection, but there aren’t many left. He leaves on his horse and visits the medical center that has settled down on an old fast food building. There he meets doctor Gladys, who is trying to find a cure.
She gives Singh more medicine for Rani and shares her notebooks so he can help her keep track of what works or doesn’t. Gladys reveals she has cancer and wants Singh to continue to search for a cure since she can’t work anymore. Back in the house, the mother notices Tommy has a Last Man mark on his chest and confronts him in private.
Tommy explains he isn’t a Last Man anymore and he only used to kill to survive. He also thinks it’d be a good idea for the family to adopt Gus. Later when the mother sees Birdie’s picture, she identifies the place as Red Rocks.
In the middle of the night, Gus can’t sleep and discovers Tommy is about to leave alone. At that moment the Last Men arrive and ask the family to give them the hybrid. Tommy goes outside and starts fighting them with a bear trap, easily bringing them down thanks to his big size.
A man manages to sneak into the house and tries to shoot Gus, who dodges just in time. Then Gus quickly stabs the man in his leg and gets ready to defend himself with his slingshot, but the man freezes when a huge deer appears at the door. Tommy uses the chance to sneak behind the guy and kill him with the bear trap while the deer disappears.
The next morning, the family kicks the duo out to protect their son, but at least they share some provisions. Tommy agrees to take Gus to the train station, but afterward he must search for his mom on his own. In an abandoned amusement park, a group of teens who call themselves “Animal Army” are playing videogames.
Suddenly an alarm alerts them of “hybrid distress”, so they leave to take care of it. While Tommy and Gus continue to travel, they come across some flowers that Gus never saw before. Tommy explains they appear in areas where the virus is.
When night falls, they stay in an abandoned bus where Tommy keeps his supplies, his medicine, and his old trophies. Gus goes to bed and is startled by a bright light outside, so he comes out and discovers there’s heavy snow everywhere with no Tommy in sight. At that moment Gus wakes up and realizes it was a dream.
Tommy has made a disguise to make it look like Gus’ antlers are part of a costume. In the meantime Singh takes over Gladys’ practice and sees patients every day, which reminds him of how much he loved being a doctor before the outbreak. After work hours, he continues to work on a cure and his wife becomes his control group since she’s the only person who has survived the virus.
Reading Singh’s notes reveals that her research was immoral and she did lots of experimentation on hybrids, proven by the blood stains on the floor. The Last Men bring supplies for the clinic and Singh is worried they may include hybrid parts, but the boxes are normal. Since Singh refuses to use hybrids for the medicine, it isn’t as effective anymore and Rani’s hand is constantly shaking.
She convinces him to go to a neighbor’s party anyway, which is interrupted when one of the men reveals a shaking hand too. The neighbors immediately hold him down and use a home test on a sample of his blood, which confirms he’s infected. The group immediately ties him up and burns the whole house with him inside.
Back to Tommy and Gus, they reach a bridge and see a train pass by. They follow it to the station and Tommy bribes a guard with some batteries to avoid being scanned. There’s a big market in the station and Gus enjoys the food while Tommy buys the ticket.
Since it’s so expensive, he has to hand in his shoelaces as part of the payment. Tommy also tries to buy more medicine, but the supplier is gone. Gus goes wandering around and finds kids playing some carnival games, but he gets upset when he realizes the targets are drawings of hybrids.
As he panics he bumps into Becky of the Animal Army, who helps him calm down and pokes his ears. She tries taking him with her, however Tommy immediately drags him away. Afterward Tommy gives Gus the ticket and takes him to the boarding line.
While waiting, Gus smells Tommy’s medicine coming from some boxes so Tommy asks for his help. Following Gus’ nose, they break into the security car and take a box of medicine. A guard finds them and Tommy quickly brings him down, but when they come out another armed man threatens them with his gun.
Tommy starts fighting him and before passing out, the guard notices Gus’ ears moving. The duo runs away and rushes to catch the train, only for the Last Men to surround them and capture them both, removing Gus’ helmet to confirm he’s a hybrid and taking back the medicine. Moments later, the duo is being dragged through the forest with their hands tied and their eyes covered.
Suddenly someone opens fire from the shadows and soon the Last Men are being killed by Becky and the Animal Army, who are wearing animal disguises. Meanwhile at the Last Men headquarters, the leader General Abbot is informed someone very important has been found. In the forest, Becky explains that they don’t want to hurt Gus, they just want to help and advices him to run away from Tommy.
The others are tasing Tommy down and get ready to shoot him, however Gus hugs him as he begs them not to do it. Becky agrees to help them both. In the zoo, Aimee lives with the baby, who has grown into a young girl named Wendy.
They go to town together with a wagon to look for supplies, but Aimee gets scared when she sees a burning cigarette on the ground. She drags Wendy to hide and takes out her gun while a Last Man passes by, thankfully he doesn’t see them and leaves. When the duo returns to the zoo, Aimee locks all the doors.
Sometimes Aimee notices there are vegetables missing from the garden, and Wendy claims she ate them. However when her mom isn’t looking, Wendy drops some of her dinner in the garden. One night they hear some noises and Aimee goes to the garden with her gun.
She hears another noise and gets ready to shoot, but Wendy runs in and explains that’s her friend Bobby. He’s also a hybrid and Aimee has no choice but to keep him too. This causes her to change her rule of not using the radio and starts broadcasting that she has a safe heaven for hybrids.
Back to the forest, the Animal Army takes Gus and Tommy to their hideout in the amusement park, which is decorated with animal drawings. Becky explains she started this group and nobody here has parents. Then she introduces Gus to the other teens, who are excited to meet a hybrid.
Gus is declared king for a night and gets to enjoy new candy, cartoons, and games. Becky tells him how the adults ruined the world before The Crumble and how the planet has been healing since then. The Animal Army thinks this is thanks to the hybrids and that’s why they fight to protect them.
The Last Men killed Becky’s parents and that’s another reason why adults aren’t allowed in their base. She tells Gus that Tommy has the Last Man mark too, so he shouldn’t trust him. The next morning Becky takes Gus to see Tommy, who has been tied up and gets tased whenever he gets sassy.
Under Becky’s pressure, Tommy admits he used to be a Last Man to survive but swears he isn’t anymore. Gus points out the Animal Army also killed people to survive and hugs Tommy, which convinces Becky not to kill him. She makes a big announcement but the other teens disagree and open a container that reveals a huge hungry tiger ready to execute Tommy.
Gus runs ahead and asks the tiger not to hurt anyone, causing the beast to back away in fear. Some of the teens see this as a sign and close the container, but others still want the execution and the argument escalates into an actual fight. Gus uses the confusion to free Tommy and they run away together, while Becky also chooses to leave her friends behind.
In town, Singh is worried about Rani’s condition because the medication isn’t working. Rani has seen Gladys’ notebook and begs her husband to start using hybrids for his research so she can get better. On his way to work, Singh sees all the flowers that have appeared at the burnt house.
At the clinic, Singh reads Gladys’ notes on which hybrid parts are needed and takes the flare gun, which has different colored flares depending on what he needs. Singh shoots the one asking for “the special sauce” referring to hybrid parts. When he returns home, he sees a flower on his garden.
Inside she finds Rani talking to a neighbor who wants to start mandatory weekly virus screenings for the whole town. Singh refuses to do so because tests are scarce, but the neighbor promises to make the community vote. Sometime later the neighbor realizes Rani doesn’t go out anymore and yells at the couple for hiding her illness.
Singh tries to stop her from telling everyone and while they argue his horse accidentally kicks the woman, killing her. Singh feels guilty but Rani convinces him to bring the body into the house. That night Abbot and his men burst into Gladys’ home.
Abbot accuses Gladys of faking her cancer to avoid working with him and explains that there’s a new virus wave coming. Gladys calls him a monster but when he threatens her life, she has no choice but to admit she left her notes on the cure with her replacement at the clinic. Then Abbot sends his men to kill her anyway.
In the forest, Tommy is having lots of leg pain because of his lack of medicine. He thanks Gus for defending him and teaches him to fistbump before announcing he’ll take him to Colorado. Suddenly they find Becky on a tree, who gives her the address her former team found from Birdie on the internet.
Then she offers to help them reach Colorado since she knows what areas the Animal Army doesn’t patrol. The trio walks for a few hours and stops when they find some fabric on a tree. Tommy explains it’s a parachute and thankfully Gus doesn’t see the body hanging from another tree nearby.
Eventually they reach the Valley of Sorrows, which is covered in the virus flowers because bodies used to be buried there. They’ll have to use a bridge to cross, which causes an argument between Tommy and Becky over its safety. Gus ignores them and starts crossing alone, causing some wood to break.
He falls and grabs onto the rope at the last second, however the rope also breaks and Gus falls on the flowers, passing out. His old dog plush appears and licks him until he wakes up, then it runs away. Gus chases after him and enters the forest, where he sees the flowers on a tree and a mailbox that ejects candy.
Then it starts snowing and Gus finds many objects, like beds and hot chocolate. Richard appears on a chair and says he isn’t mad that Gus crossed the fence, he also points at train tracks nearby. Then Richard disappears and an angry Gus starts hitting a mirror, where he sees Abbot’s face with fiery eyes.
A terrified Gus starts running, only to wake up when his friends find him. By covering their faces, they manage to take Gus away from the flowers without inhaling their pollen. Then Tommy and Becky start arguing again, so Gus makes them fistbump to shut them up.
At the zoo, the family has been growing thanks to the other hybrids that have arrived after hearing the broadcast. Aimee gets a call from a man who found a hybrid baby and asks for advice on how to take care of them. She tells him to leave the baby on a safe spot to pick them up, but the man refuses because the baby is too weak and asks where she is.
Thinking it may be a trap, Aimee hangs up. Afterward Bobby brings a ribbon that he found on the fence, meaning they’ve been marked. In town, Singh has to pick all the flowers that appear on his garden.
A neighbor is now putting up missing signs for the missing woman and Singh has a hard time keeping a straight face. One afternoon, he gets a message from the clinic saying a package has arrived for him. The couple rushes to the clinic eager to start working with the “secret sauce”, but when they open the box they find a note that says “out of hybrids”.
At that moment Rani notices water leaking from the freezer and go inside to confirm the neighbor’s body is still there. However the door is open, which means someone saw it. At that moment the neighbors arrive and accuse the couple of being killers.
Singh starts lying, saying the woman had been sick and he hid her because he doesn’t approve of the burnings, seeing them as barbaric. His speech makes an impact, but it’s ruined when Rani begins to cough. The neighbors drag the couple back to their house and tie them up before starting the fire.
The house starts crumbling down, however before the flames can reach the couple, the Last Men burst in. They quickly put out the fire while Abbot searches for Gladys’ notebook, finding it in a cupboard. He’s about to leave without saving the couple, but he freezes when Rani reveals she’s survived the virus thanks to the trials.
Gus lies as he says he’s the only one that knows what Gladys was missing for a proper cure, so Abbot agrees to bring them along. Since the headquarters are in a classified location, Rani and Singh are tied up and have their faces covered before they’re put in a truck. Meanwhile Singh’s horse runs away.
Back to Gus’ group, they finally find the tracks and start running to catch the train. There’s a hook hanging on the side of the car and Gus jumps to grab it, swinging to jump into the train. Becky manages to jump in as well, but Tommy is having trouble because of his leg.
He remembers how hard he used to run for football matches and inspires himself to grab on the train at the last second. The kids help him up and look around the train, discovering this is a hauler so it has no passengers except for the working crew. They don’t notice a Last Man uniform behind a door.
During the trip, Gus is amazed to see all the animals and Becky teaches him to play “I spy”. When Gus checks his bag, he realizes his dog plush is missing. At that moment the door opens and the trio rushes to hide.
A worker comes by and at first he doesn’t see them, but when Gus accidentally drops a bottle the man finds him and pins him down. Tommy attacks the man from behind and a fight ensues during which they almost push Becky off the train. After lots of punches, Tommy takes a better look and realizes the worker is his old friend Jimmy, so they laugh and hug.
After they share some stories from their football days, they realize Gus has gone looking for his dog. The trio searches for Gus while Jimmy keeps asking about Tommy’s life. It’s revealed that all their old football teammates, Tommy’s wife, and his baby are dead.
At that moment Gus comes back looking sad because he couldn’t find his dog, which is the last thing he has with Richard’s smell. Tommy cheers him up by showing him a river that indicates they’re arriving at Colorado. The address from the internet mentioned “GoGro” and Jimmy explains it’s short for Goss Grove, a neighborhood outside Essex City.
The chat is interrupted when Becky hears Last Men in the other car and Jimmy takes the group to the back area, however they can see the men coming. Becky thinks they should jump, however Tommy sees the dog and decides to rescue it. He puts on the uniform from the door and pretends to be a Last Man to pick up the dog.
However the men have a wanted sign with Tommy’s face and recognize him. Tommy throws a bunch of boxes to slow them down and runs back to Jimmy’s car, closing the door behind him. The Last Men soon start pounding on it, so Jimmy tells the trio to jump while he buys some time.
After a final goodbye, Gus’ group jumps off the train at the same time the Last Men burst in. Jimmy starts fighting them but he quickly gets overpowered and killed. At the zoo, Aimee finds a bunch of ribbons at the fence and announces they must leave.
Suddenly they hear a noise and check the security cameras, which show two Last Men outside. They immediately pack up their things and Aimee guides all the hybrids to escape through the sewers, but she stays behind in case the Last Men need to be distracted. A flashback then shows that in Alaska, an expedition team discovers something very important in one of the many ice rods they extract.
This is sent to a lab in Essex City where Richard works at as janitor. One afternoon, he hears scientists Birdie and Judy arguing. Birdie says they can’t “let this happen” but they fall silent when they see Richard nearby.
Later at the pub, Richard spots Birdie and apologizes for what happened. They spend a wonderful night together and Birdie ends up sharing a bit about her project. The people in Alaska found a microbe that could form a vaccine and save lives, but if it goes wrong then all hell could break loose.
Afterward Richard walks Birdie home and she invites him in. Birdie shares that her husband died from a serious disease and that’s why she stopped teaching to start researching. When they’re about to kiss, they’re interrupted by an urgent call informing Birdie that the military is taking over the lab.
Richard volunteers to drive her there and they go inside through the back door. There are lots of soldiers taking away all the research, but the duo takes an empty corridor into a secret office. Birdie shows Richard that their experiments with the microbe have created a miracle and reveals baby Gus, who starts crying.
The soldiers hear it and appear on the corridor, so Birdie wants to escape with the baby before the military finds him. Richard puts on his janitor clothes and pretends he’s cleaning to distract the soldiers, allowing Birdie to sneak out with the baby. After the men let him go, Richard runs to meet with Birdie, who hands Gus to him and asks him to keep him safe while she goes back to burn all her research.
When she steps back, a fence closes between them and an alarm starts wailing, so Richard runs away with Gus. In the present, Gus’ group finds Essex City. After wandering around they find the right house and Gus pounds on the door, asking for Birdie.
The person opening the door is Judy, who recognizes Gus and is shocked to see he’s alive. She explains she used to work with Birdie and that she came to this house looking for her, but she only found the military ransacking the place. The soldiers beat Judy up and left her for dead, later she was found by Birdie who nursed her back to health.
One night Birdie just left, and Judy doesn’t know where she is now. Gus notices a pot with the lab’s name and recognizes it from that ID he found in Richard’s box. Judy gives Gus a key to the attic that Birdie had asked her to protect.
Gus is excited to open it, but Becky and Tommy worry because they recognize the name of the lab from the rumors of where the virus came from. They enter the attic and Gus finds a picture of Birdie with her father while Becky discovers some files with Gus’ name. It turns out "GUS" stands for "Genetic Unit Series" and the pictures in the files reveal the truth.
Gus freaks out so Becky explains she was also adopted, but that doesn’t mean her parents weren’t “real”. However Gus keeps on getting angry because Richard lied about everything and he rushes out of the house. As he runs through the forest, a bunch of deer run with him.
Another flashback shows that in the early days of the outbreak, one of the essential workers is accidentally hit by car. The driver is Tommy, who is desperate to get his wife into the hospital because she’s about to give birth. The place is full of patients and at first the soldiers and nurses don’t want him to stay, but after some begging they take Tommy’s wife to the maternity ward.
While waiting, Tommy sees on TV how hybrid births are on the raise and people protest about them on the streets. A few hours later, Tommy is informed his wife gave birth to a boy, but when he checks on him he discovers it’s a hybrid baby. He immediately runs out of the room and has a panic attack before getting into the elevator, where Singh offers supportive words.
In the present, Tommy and Becky search for Gus to no avail. Becky admits she feels confused because all her life she though hybrids were nature’s miracle, but now they appear to be just a lab experiment. Tommy tells her to wait in the house in case he comes back and goes looking for Gus more deeply in the forest.
Meanwhile Gus is getting rid of all the things Richard gave him, including Birdie’s picture. At that moment he finds a bunch of flyers promoting the hybrid preserve on the ground and a plane outside the forest. While Gus looks around, Tommy arrives and gives him the dog.
Gus says he has no dad and that he wants to go to the preserve to be with others like him. Tommy shares the story of his hybrid son and how he almost ran away, but he realized he was only scared of being a dad so he went back for his wife and baby. However when he returned, the soldiers had already killed them both.
He asks Gus not to abandon him too, but Gus reveals the plane’s radio is working and he already called the preserve. Suddenly they hear a shot and Tommy collapses while they’re surrounded by Last Men, who put Gus in a cage and take him away. Back in the sewers under the zoo, the hybrids hear how a bunch of Last Men arrive in the city with tons of trucks and even tanks.
Abbot tells Aimee to hand over the hybrids, but she refuses and starts a speech on how the hybrids are better than humans, which is heard by the kids. As the men surround the zoo, Aimee activates a bunch of fireworks that keep the soldiers distracted while the kids continue to cross the sewers without being heard. While the Last Men break into the zoo, the hybrids make it to an abandoned church.
Bobby wanders off and is found by soldiers, who immediately capture him and take him away. Wendy tries sneaking out, however she’s quickly found and captured as well. Moments later when Aimee arrives at the church disguised as a Last Man, she screams in grief when she discovers all the hybrids were taken.
In the meantime, Singh and Rani arrive at the Last Men’s headquarters. Rani is immediately isolated and Singh freaks out in anger, but the soldiers grab him and Abbot tells him they’ll let Rani go after Singh finds the cure. Sometime later, the men bring Gus in the cage and Singh gives him some candy.
When Gus says “thanks”, Singh is left in shock at his intelligence. He announces he wants more time with Gus so he asks for another hybrid to work on for now. Back in Judy’s house, Becky admits her parents weren’t actually murdered, they were killed by the virus.
Her sister had been a hybrid, and the Last Men took her away. For a long time Becky was alone trying to find her sister while growing to hate adults. Eventually she found other kids in her same situation and they formed their own family.
At that moment Judy’s radio gets an important message and Becky sends one back, finding Birdie on the other end. At the same time a mysterious person picks up Tommy and the dog plush in their truck. In the Last Men’s headquarters, Gus is sent to a warehouse and watches how another hybrid is taken away.
There he meets all the kids from the church, including Wendy and Bobby who give him a big hug. The taken boy is soon killed by Singh in his lab for the sake of the cure. Tommy wakes up in a strange apartment and finds Aimee, who tells him they’ll rescue their kids soon.