A decade later, the American Division is testing a potentially deadly augmentation drug on a "Pusher", named Kira (Camilla Belle). The test appears to have failed, until the doctor checks Kira's pulse and she reveals herself to be alive (the one and only survivor). Rendering the doctor unconscious, Kira steals his security clearance card and an augmentation drug-filled syringe. She escapes with the help of her enhanced abilities and interference from a nearly-catatonic "Watcher".
In Hong Kong, two days later, an adult Nick Gant (Chris Evans) is hiding from Division as an expatriate. He attempts to use his ability to make a living, but his poor skills at "moving" render his attempt to fix a local dice game unsuccessful, leaving him indebted to a local Triad, incidentally, controlled by "Bleeders", bred by the now-defunct Chinese Division. After escaping from the gamblers, he returns to his apartment to find that the American Division has located him. Two "Sniffer Agents", Mac and Holden (Cory Stoll and Scott Michael Campbell), demand to know if he has met a certain girl. While Mac sniffs around Nick's apartment, Holden psychically "reads" Nick's actions in this apartment, ascertaining that he has not met the girl. The two Agents leave, taking Nick's toothbrush in case they need to find him again.
Almost immediately, a young girl named Cassie Holmes (Dakota Fanning) arrives at Nick's apartment. Cassie explains that she is a "Watcher" and that they are going to find a case containing $6 million dollars. Nick and Cassie go to a restaurant to further discuss their plans. As Cassie tries to convince him to help her, she has a vision and proceeds to run ahead, claiming that trouble is near. The two are caught and subdued by the Triads. Nick helps Cassie escape and as the Triads' "Bleeders" prepare to kill him, they are stopped by their sister, a "Watcher" (Li Xiaolu), who states that without Nick, they've no chance of finding the girl. As Nick lies on the ground, dying, an unknown woman comes and retrieves him. Cassie follows and finds an unconscious Nick lying face-down on a table. The woman who rescued him, a female "Stitcher" (Maggie Siff), heals his wounds to repay a debt she owed to Cassie's mother, a prolific "Watcher" who has been imprisoned by Division. As Nick reawakens, Cassie gives him a lotus flower and he recalls the words of his father, and chooses to help Cassie.
Meanwhile, Kira is captured by Agents Mack and Holden, but manages to escape by pushing Mack into shooting his partner. Carver, in turn, pushes Mack to shoot himself for his mistake. Nick and Cassie go to a nightclub on a hint from Cassie's predictions. Upon entry, Nick sees an old friend, "Hook" Waters (Cliff Curtis), who happens to be a "Shifter", using his abilities to swoon local ladies and scam the club. He uses his abilities to make a replica of the clue in Cassie's drawing and he tells them to go to Emily Hu (Ming Na), a highly skilled "Sniffer" who can help them find Kira.
After Nick and Cassie find Kira, who used to have a romantic relationship with Nick. Kira was captured by Division and Nick failed to find her. They recruit a "Shadow" named "Pinky" Stein (Nate Mooney) to hide Kira from the "Sniffers", knowing that it is merely a stopgap measure; a "Shadow" cannot hide a subject from a "Watcher" under any circumstances, but only from "Sniffers" and only for a short time. The Division has several tracking Kira. Later that evening, Nick and Kira manage to rekindle their relationship while Cassie walks around town by herself, confronting the Triads' "Watcher" and receiving threats from her.
When Nick returns, he finds Kira in poor condition and understands that Carver told the truth regarding the drug's side-effects. As he comforts her, Cassie barges in and, thanks to one of her drawings, finds the key to a locker in which Kira hid a valuable case. With the aid of Cassie's visions, they are able to roughly piece together the events that led them to meet; Cassie's mother used her visions to set a complex plan in motion that will lead to the destruction of Division. Knowing that they are being tracked by "Watchers" from both Division and the Triad, Nick comes up with an elaborate plan that involves seven envelopes in which he places instructions; each person in the group is entrusted with one envelope, and none are to be opened until the time to act is right.
First, Pinky pretends to betray Kira, but, then, turns the reward (though he is somewhat disappointed he does not get to keep the money for his efforts) over to Nick. Nick uses the money to pay a "Wiper" to erase his memories of the plan, ensuring that Watchers from both Division and the Triads will no longer be able to interfere.
Hook retrieves the case (which does not have $6 million dollars, but instead has the syringe Kira stole) and brings it back to Cassie and Emily. He shifts another case to look exactly like the case with the syringe. Cassie then takes the shifted case to Nick's apartment, following his instructions, and waits. Nick regains consciousness: he has no memory of the envelopes or his plan,just as he had planned. He opens his own envelope, which simply tells him to return home, which he does. When he returns home, he finds the case in his room. The female "Stitch" who healed him returns the injuries he received from the "Bleeders" earlier, and he collapses in agony. The "Stitch" hands over the case to the "Bleeder" Triads, who, in return, pay her. As she prepares to leave, Nick, using his abilities to take the guns Cassie had hidden (as she was instructed), holds the "Stitch" at gunpoint, forcing her to heal him. Meanwhile, after Budarin injects Kira with an immunosuppressant to counteract the adverse effects of the drug, Carver introduces himself to Kira as a friend, stating that her memories are false; she is actually a Division agent who volunteered to take the augmentation injection, and suffered memory loss as a side-effect and shows Kira her badge.
As Cassie and Nick leave the "Stitch" tied up in his apartment, Cassie fears the worst because of all of her drawing which have to do with her death. Nick promises that she will not die and the two depart.
Cassie finds her hiding place in a large apartment building, but, the Triad "Watcher" finds her and holds her at gunpoint. Prepared to kill Cassie, the "Watcher" tells Cassie that she made her look like a fool in front of her family. Before she is able to pull the trigger, the "Wiper" that wiped Kira and Nick jumps out and easily wipes all of the Watcher's memories.
Nick goes to retrieve the augmentation drug himself and confronts Carver, Kira and Budarin. Kira reveals that she has been using Nick the entire time and Nick, defeated, takes the three to the building which contain the lockers and the case. Nick is captured as Kira, Carver and Budarin proceed to obtain the case. As they do, they are, suddenly, ambushed by the entire group of Triads. Budarin, Kira and Carver effortlessly defeat most of the Triad's forces and, unintentionally, free Nick from the car. He joins the large battle, commencing a rematch with Budarin. As Nick finally overpowers Budarin, both are attacked by a "Bleeder" Triad. Budarin manages to kill the "Bleeder" with a bamboo stick thrust through his neck. As he and Nick attempt to resume their fight, the Leader of the Triads reveals that he, too, is a "Bleeder", and kills Budarin. As the "Bleeder" continues to scream, Nick causes a very large amount of building material to descend upon the "Bleeder", successfully killing the leader of the Triads.
He rushes over to Kira and Carver to confront them. Carver beats Nick and pushes him to walk off of the roof of the building. Immediately before Nick walks off, he turns and knocks Carver to the ground, grabs the case and jams the syringe into his own arm. Carver tries to tell Nick that it's a bad idea to use the drug. Ignoring Carver's warning, Nick injects himself and apparently dies. Carver and Kira depart. Moments later, Cassie walks over to Nick's body and tells him that she had told him to bring an umbrella. Nick opens his eyes and stands up. Cassie retrieves the true case, revealing that Nick really only injected himself with soy sauce, as they had planned. The duo leaves, Cassie stating that they'll meet Kira again soon enough.
On the flight back to America with a sleeping Agent Carver, Kira opens her purse and finds her red envelope. She remembers Nick telling her to open it when "she started doubting the truth" and opens it. Inside, she finds a picture of her and Nick at Coney Island. Written on the picture is the message "KILL HIM. See you soon, Nick." Kira then pushes Carver, commanding him to put his gun in his mouth and pull the trigger. The screen fades to black, immediately followed by the sound of a gun shot.
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