Distraught by her parents’ constant fighting, Maya leaves her old life behind and moves in with her boyfriend, Dante, a struggling musician in New York City. At first she is hesitant to even step inside the condemned building where he lives, but Dante manages to coax her into giving it a chance. He explains that Shynola, the building’s elusive superintendent, still lingers there, which means the place has at least the basics—plumbing and electricity—working enough to keep them going. The place is home to a motley mix of residents beyond Shynola: Alexa and Loki, Dante’s roommates; Roxy and Big Foot, a transgender sex worker and her pimp; Tess and Vince, once-hip junkies trying to stay clean; Cookie, who runs a meth lab out of his corner of the building; Gault and Murphy, two death metal enthusiasts who practice a blunt form of S&M in their own space; and Hoobler, a reclusive figure who keeps largely to himself.
Maya finds herself getting along with most of the residents, but she quickly clashes with Gault, who threatens her with harsh warnings about her naivety—warnings he says could bring police scrutiny and invite a raid. After Loki showers, his roommates initially fear he’s ill, but his fever spirals into violent hallucinations and erratic behavior. Maya wants to call the authorities for help, but Gault objects, and Dante stops her, accidentally destroying her cell phone in the process. As the night unfolds, Maya and Dante notice an unsettling shift in the other inhabitants’ behavior. Years of poor plumbing have left the building’s tap water contaminated with toxic chemicals and diseased refuse, a mix that fuels violent psychosis among the residents.
Cookie steps out to deliver a new batch of drugs, bolting the doors behind him to keep potential trouble out. Two police officers, inexperienced and clumsy, fatally shoot Cookie, leaving the inhabited building effectively trapped with the growing crisis inside. Dante enlists Vince to help search for Loki, who has vanished somewhere in the maze of hallways and stairwells. Meanwhile Alexa grows more violent, and Maya defends herself when Big Foot attacks Roxy, knocking the assailant unconscious. The situation deteriorates further as Vince stabs several people in a panic-driven effort to contain the spread of infection, and Tess, who rants about gentrification, is killed by Big Foot amid the chaos. Murphy and Big Foot exchange brutal blows, and Maya uses the distraction to slip away and reunite with Dante.
Together, Maya and Dante venture through the building in search of anyone still uninfected, hoping to find help or a way out. Instead they encounter more violence and desperation as former friends turn on one another. Murphy corners them, forcing a confrontation in a bathroom. He is killed by his lover, Gault, in a tragic moment of cross-purposed violence. Maya escapes through a small hole in the wall and retrieves a weapon for Dante, preparing for the worst. After a tense confrontation, Dante becomes trapped in rotted flooring and pleads with Maya to flee as Gault closes in. Dante falls through the floor, leaving Maya to face Gault alone. Hoobler suddenly appears in a hazmat suit and shoots Gault, ending the immediate threat. Hoobler urges Maya to contact the authorities, but Loki then makes his appearance, killing Hoobler and chasing Maya into the sewers beneath the building.
Dante and Maya press on deeper into the sewer system, their progress hampered by Dante’s injured foot. They eventually come face to face with Loki; in a fierce struggle, Dante kills Loki but contracts an infection in the process, turning increasingly hostile toward Maya. Desperate, she runs to a sewer grate and calls for help. The officers who had killed Cookie earlier observe her from a distance, and she loses consciousness. When she awakes, she finds herself in a hospital, crying out for Dante as the room fills with unsettling, hallucinatory imagery involving the attending doctors. A CDC official then orders the entire block quarantined. In the dim corners of the sewers, Dante is glimpsed wandering, his fate still unresolved as the system shuts down around them.
