A few years after their previous encounters, a new school year begins at Crestview Academy, bringing fresh tensions and unresolved mysteries. Siouxsie Hess, a teenage girl with a rebellious streak and a Gothic style, is now a sophomore. She is determined to stir up trouble and make a mark, eager to get into Saturday detention with the senior students. Her attempt to join the senior class’s punishment is assisted by her acquaintance, Drake Bell, known as "The Naked Wizard", who confidently assures her that her goal will be achieved by the time she arrives at school.
At Crestview, Sean Astin plays Headmaster Nash, a strict authority figure, who becomes involved when Siouxsie vandalizes the headmaster's car out of frustration. Nash responds by assigning her to see [Sufe Bradshaw] as Dr. Knight, the school secretary responsible for managing student punishments. Despite being tasked with overseeing discipline, Dr. Knight’s role becomes more complicated when she receives an email directive from Nash to send Siouxsie to Saturday detention, igniting suspicions of deeper plans.
The plot thickens during a chaotic, drunken party attended by the senior students, where tragedy strikes. Siouxsie’s older sister, Ashlyn McEvers portraying Alison Hess, unexpectedly jumps off the school’s roof, plummeting to the street below. Her death, initially presumed a suicide, is met with disbelief by Siouxsie, who begins to investigate what really happened. Convinced that her sister's death was no accident, Siouxsie becomes fixated on uncovering the truth behind the mysterious circumstances surrounding Alison’s fall, turning her grief into a quest for justice.
The story then focuses on the detention session scheduled for that weekend, where Siouxsie, along with a group of fellow students—Matthew Frias as "Latin Spice" Brian Marquez, Erika Daly as "Cat Lover" Sara Hasegawa, Sophia Taylor Ali as "Preacher's Daughter" Faith Jackson, and Colby Arps as "Mr. Clean" Blaine Wilkes—arrive for their detention. Their arrival is marked by the confiscation of their cellphones and the realization that all school doors now operate on a security passcode, heightening their feeling of being trapped. Despite efforts to access the library, the doors remain locked, even when janitor Ben Browder attempts to input the codes, suggesting that something more sinister is at play.
As the students wait inside, the tension escalates. Siouxsie secretly follows Max, the janitor, to the maintenance workshop and notices strange behaviors and insect infiltration, hinting at something ominous lurking within the school’s systems. Using a stun gun on Dr. Knight, she detains her temporarily and steals her access code and a flash drive containing a virus from a computer in the lecture hall. Unbeknownst to her, this virus triggers chaos. It activates the school’s lockdown, and steel gates slam shut, trapping everyone inside.
The students quickly realize the danger when Erika Daly's character, Sara, discovers the virus and, after using cocaine, panics as she begins to vomit blood and dies unexpectedly. Following this, the security measures cause metallic barriers to close, cutting off escape routes. Desperation grows as they search for a way out, with Faith heading to the science lab for help. Meanwhile, Sara’s body is found in the security garage, heightening the horror.
In the chaos, Siouxsie sneaks into the industrial arts room, attempting to find a way to escape. During this effort, she unwittingly pulls down a power saw which injures Colby Arps as she seeks a welding torch. This accident results in the horrifying death of Sara, who is impaled by the active saw, leaving the group devastated. Tensions between Siouxsie and Colby Arps's character, Blaine Wilkes, come to the fore. Blaine reveals murderous motives connected to his sister’s death, blaming Gina Gershon as his mother, Senator Wilkes, who helped fund his revenge plot. Blaine admits to pushing Alison off the roof, poisoning Brian to cover his tracks, and disabling the power to the deadly drill that caused Sara’s death.
The confrontation worsens when Blaine attempts to frame Siouxsie for his crimes. Faith starts to believe Siouxsie’s innocence but gets caught in Blaine’s trap, which leads to a terrifying auto shop sequence. Blaine ties Faith in a noose, rigs a car, and in a tense montage, She tragically dies, as Blaine's brutality is fully revealed. Siouxsie manages to break free and witnesses a devastating scene that pushes her to the edge.
In the climax, Siouxsie cleverly fights back—driving a garage jack to crush Blaine’s legs, setting the school ablaze, and escaping the chaos. A SWAT team arrives to find her fleeing through the school, armed with a makeshift flamethrower. As they confront her, she defends herself fiercely, torching an officer and fighting for her survival. The story concludes with her finding refuge in the football stadium, where she continues her desperate fight against her pursuers.
A final scene after the credits shows Sean Astin and a woman, Alexandra "Ali" Astin, discussing a shooting incident involving Nash and Ethel, raising questions about the larger conspiracy behind the school's dark events. The film leaves viewers with a sense of lingering mystery, hinting that the horrors at Crestview Academy might not be entirely over.