As nuclear explosions ravage New York City, the apartment block residents rush downstairs to escape the building, only to be forced into the basement by further explosions. Only eight of the residents, Eva (Lauren German) and her boyfriend Sam (Iván González), Josh (Milo Ventimiglia) and his brother Adrien (Ashton Holmes), Josh's friend Bobby (Michael Eklund), Marilyn (Rosanna Arquette) and her daughter Wendi (Abbey Thickson), and Devlin (Courtney B. vance) manage to force their way into the buildings bomb shelter before the superintendent, Mickey (Michael Biehn), seals the door. The group acclimate to the cramped surroundings while Mickey asserts his dominance of the shelter, to the chagrin of Josh, Bobby, and Devlin. After time passes, the shelter's door is broken open and the shelter is invaded by armed soldiers in biohazard suits; the men's speech is unintelligible, and their allegiance remains ambiguous. The men attack the group and seize Wendi, leaving the shelter with her. Devlin and Mickey manage to kill two of the men, and Mickey takes his machine gun. Josh volunteers to use one of the dead soldier's suits to leave the shelter and search for Wendi.
Outside of the shelter, Josh finds the area entirely sealed off by material tunnels connected to a laboratory. His outfit allows Josh to explore the lab, where he discovers several children, including Wendi, in containment units, seemingly unconscious, their hair shaved off and their eyes covered with plasters. One of the soldiers checks the ID on Josh's outfit and, realizing he is an impostor, tears out his breathing apparatus, exposing Josh to the air. Josh flees back to the shelter, killing two of the soldiers on the way. After Josh returns, the soldiers weld the door shut from the outside, trapping all within. Time passes; Josh begins to suffer the effects of his exposure and admits to Adrien that he only went outside to find rescue for Adrien and himself; Eva, in a fractured relationship with the meek Sam, grows closer to Adrien; Bobby is forced to hack up the bodies of the dead soldiers so their decaying remains can be flushed away; Devlin grows suspicious that Mickey is hoarding resources; and Marilyn, told her child is dead by Josh, enters a sexual relationship with Bobby.
Marilyn attempts to convince Eva to sleep with Josh, warning her that the men will want sex. The group grow increasingly angry with Mickey as resources grow scarce, culminating when Devlin discovers Mickey's locked safe room and threatens him with a taser to open it. A scuffle ensues and Mickey shoots Devlin dead with the machine gun. The group do not believe Mickey's argument of self defense and an increasingly ill Josh, and an increasingly deranged Bobby, torture him to gain the code to the safe room; Eva throws the machine gun into the toilet septic tank to stop Josh using it. Seizing authority, Josh and Bobby are physically and emotionally abusive of Marilyn. Josh makes it clear that he wants Eva, and Sam is unable to stand up for her. Eva and Sam try to protect Marilyn from Josh and Bobby, but are unable to. While Eva is tasked with watching Mickey, Mickey reveals that there is a gun hidden in his safe room.
Josh and Bobby force Eva to hack up Devlin's corpse when Sam cannot, leaving Eva distraught. Josh and Bobby, both losing their hair to illness, shave their heads. Mickey informs Eva that there is another way out of the shelter; through the septic tank. Eva tries to retrieve the gun, but cannot get past the pair. She finds Marilyn's corpse, the two having beaten her to death. Eva notices her hair is falling out and realizes she is also sick; the shelter is not protecting them from the outside because of the broken door. Eva sends Sam to retrieve the gun while she cuts the power to distract Bobby and lures Josh away with the promise of sex. Josh grows suspicious and tries to rape Eva, but she fights him off with help from Adrien. Sam retrieves the gun, but as Bobby, Josh, Eva, and Adrien yell instructions at him, Sam shoots and kills Adrien. Josh brutally beats Sam. Bobby turns on Josh and is about to shoot him when Eva cuts his throat with a tin can lid. Eva frees Mickey who shoots Josh. Josh smashes an oil lamp, setting himself alight and causing a fire in the shelter. While Sam and Mickey attempt to put out the blaze, Eva chooses to escape. She recovers the biohazard suit, and locks herself in the safe room. She breaks through the toilet into the septic tank below, while Mickey and Sam are left trapped and succumb to the growing flames.
Eva emerges from the septic tank into the remains of the city and stares blankly at the devastation.