Two months after the destruction of both the Primatech and Pinehurst, and the death of Arthur Petrelli, the now-villainous Nathan returns with a vengeance by persuading the U.S. President and the government to round up all people with abilities for containment and disposal, leading to Claire, Ando, Peter, as well as Tracy to become fugitives from the people who were their former allies. In Japan, a powerless Hiro tries to live through the super-charger Ando as his latest partner. In New York, Peter struggles to find a life for himself as a paramedic, but finds that his cannot hide from his past. Claire learns about Nathan's and Angela's plans for interment of people with abilities and sets out to warn Matt Parkman who learns more about his abilities from the spirit of the African spiritualist Usutu. Elsewhere, Syler travels to Baltimore to locate his long-lost father and ends up being the only one who escapes from a government dragnet led by a mysterious agent known only as 'the Hunter'. Mohinder also learns that he has been targeted, and that Noah Bennett is apparently working with Nathan as well.

Following the plane crash, the surviving heroes must team up with one another to try to survive the manhunt. Claire is quickly captured by Noah who takes charge of a "kill squad" to find the remaining people with abilities while Nathan deals with the overzealous 'hunter' Emile Danko whom becomes obsessed with tracking down all people with special abilities in his own lethal way. Mohinder and a powerless Hiro must rely on Matt Parkman's spiritual guide to help them. Daphne makes contact with Ando to help her find Matt, unaware of the people now targeting them. In New Jersey, Syler takes refuge in the house of an agent and tortures him to try to get information to what's going on and he forms an unlikely alliance with the agent's son Luke Campbell. Also, Peter teams up with Tracy to look for help, while she begins having second thoughts about running.

Imprisoned inside the super-secret 'Building 26' which is Nathan's base of operations to experiment and terminate people with abilities, Tracy struggles to survive various "heat" experiments as well as wait for an opportunity to try to escape. While the ruthless Hunter Davko obsessively continues to track down the heroes with the obsession of killing them all, Nathan deals with the President of the USA who begins to investigate Nathan's activities and tactics to hunt down the "targets". Meanwhile, Syler continues his quest to locate his biological father with both help and inference from Luke Campbell, as well as government agents now after both of them. Hiro, Ando, and Matt travel to India to find a new ally with abilities to help them survive. In California, Claire faces the wrath of her father.

Peter, Matt, and Mohinder drug and abduct Noah "H.R.G." Bennet and hold him captive in a seedy motel room so Matt can interrogate him to find out more about the people hunting them down, but predictably, it does not go as planned as Benett plans to turn them against each other, while Nathan and the sadistic Danko are looking for him. Noah's background story is revealed about how Nathan approached him to help the government's plan to round up people with special powers, and his awkward alliance with Danko who has his own agenda... as does Nathan.

Following a tip from their anonymous source "Rebel", Matt and Peter hurry to rescue Daphne from the holding facilities in 'Building 26' in Washington, and to find evidence that may expose the government's plans to capture those with powers. Meanwhile, Sylar uncovers the truth about his mother after he experiences past memories of his father at a disused diner located deep in the New Mexico desert which makes him dump Luke and head off to look for his biological father. In California, Claire must find a way to sneak Alex out of her house which is under observation by FBI Agents, and Mrs. Bennet reluctantly agrees to help. Elsewhere, Danko hatches another nefarious and explosive plan of his own to trap and kill Matt. Also, Claire has a run-in with an old villain, Eric Doyle, whom she captured a while back who asks for her help to hide from government assassins after him too.

Now on his own, Sylar finally finds his biological father, Samson Gray, a reclusive, lung-cancer ridden taxidermist, to confront him with questions about his past, but soon learns that Samson is not who he appears to be. Meanwhile, Nathan continues to lock horns with Danko over the hunter's tactics to eliminate people with abilities, after he tries to frame Parkman for an attempted suicide bombing. This leads to both Nathan and Danko going behind each others back to unseat the other. Nathan becomes wary about Danko going rogue and the hunter interrogating Tracy, as well as Nathan's mother, Angela, about Nathan's own ability. In California, Claire takes Alex's old job at the comic book store where she is given a message by 'Rebel' to help out her former nemesis, the puppet master Eric Doyle, when he too is targeted by rogue agents. Also, Hiro and Ando return to California where they are led by clue from Rebel... to an infant Matt Parkman.

The identity of "Rebel" is revealed with chilling consequences - Emmy Award-Winner Zeljko Ivanek, Brea Grant and Swoosie Kurtz Guest Star.

Denko is approached by Sylar with an offer to help him to find an elusive shape-shifting person, despite the fact that they don't trust each other. Meanwhile, Peter and Angela hide out in a church where she seeks a path of redemption from everything that she has allowed to happen to her, while Bennett is put in charge of finding both of them. In Mexico, Clare and Nathan hide out in a seedy motel where she takes advantage of her own abilities to win money in a drinking shot contest when they run short on money.

Hiro and Ando set out to find Matt Parkman with his infant son, but soon learn that the infant's powers hinder their travel plans. Meanwhile, the shape shifting Sylar begins to use his new powers to harass Bennet by impersonating his wife, Sandra, knowing he will find out. An angry Matt Parkman begins investigating the sadistic Danko to see revenge for Daphne's death and learns more about his pursuer when he meets his Slavic girlfriend Alena. Mohinder learns more about his father's work about a mysterious place called Coyote Sands in which Angela and Peter make contact with Nathan and Clare where Angela takes them to the remote location where a secret about Angela's past lies buried.

Sylar begins to feel confused and more uncertain about himself when his new shape-changing powers begins to get out of control. He begins to imagine his late mother giving him advice on what to do, while Danko continues to use him to find and kill people with abilities and wants to zero in on 'Rebel'. When Sylar discovers that Rebel is in fact Micah Sanders, he saves him. Sylar decides to change his ways after figuring out that Danko is plotting a so-called 'Final Solution' to exterminate all people with abilities once and for all. Meanwhile, Parkman plans to return to his home in California with his infant son unaware that there are more kill-squad agents after him, Hiro and Ando rashly decide to make a heroic, and probably futile, attempt to make an assault on Building 26.

Nathan and Peter try to find the shape-shifting Sylar before he can make contact with the President and assume his form as well. Clare goes off to try to stop Sylar on her own, only to end up as a captive. Meanwhile, Hiro and Ando make a rash attempt at stopping time so they can break into Building 26. They hope to free those that still survive and have powers, while Danko, framed by Sylar for the murder of an agent, has a talk with Noah Bennett over their views on fighting this war. Elsewhere, Angela meets with Matt to ask for his help to save Nathan, when she has a dream about him being in danger from Sylar.

Claire, back home in California, begins attending college, but is having difficulty adjusting when a mysterious death of a student during the orientation puts her back in the spotlight. In Japan, Hiro and Ando continue their quest to help people with abilities and go so much as to advertise themselves. Meanwhile, Angela fears Nathan/Syler will discover his true identity. Matt tries to settle down back in Los Angeles and raise his son and not worry about unexpected visitors. Elsewhere, Peter is using his ability for good when a mysterious carnival clan, led by Samuel Sullivan, arrives in town which could spell trouble for him and everyone else.