In an underground laboratory, engineers Gary Sitterson and Steve Hadley analyze the repercussions of a failed ritual execution in Stockholm. Their facility, alongside one in Japan—still boasting an impeccable success rate—now carries the burden of the next attempt.
Meanwhile, a group of American college friends—Dana Polk, Jules Louden, Curt Vaughan, Holden McCrea, and Marty Mikalski—are enjoying a weekend getaway at Curt's cousin's cabin nestled in the woods. However, unbeknownst to them, Sitterson and Hadley manipulate their every move from afar, using mind-altering drugs to influence their behavior. When the group discovers eclectic items in the cabin's cellar, including the eerie diary of Patience Buckner, a past resident abused by her ruthless family, Dana unintentionally invokes a horrific curse by reciting lines from the book.
Upon being dosed with pheromones, Curt and Jules are lured into a compromising situation outdoors, leading to a brutal zombie attack that results in Jules being decapitated, while Curt barely makes it away. As Marty uncovers hidden surveillance gear in his room, he is suddenly ambushed and dragged off by a zombie. The lab technicians soon realize that the ritual in Japan has also met with failure, leading them to conclude that the American sacrifice is now "humanity's last hope."
As Dana, Curt, and Holden scramble to escape in their RV, the lab intervenes by triggering a tunnel collapse that seals their exit. In a desperate bid, Curt attempts a daring motorcycle leap across a ravine, only to meet his demise against an invisible barrier. Driven by a grim realization that their ordeal is manufactured, Dana fights to survive while Holden tragically meets his end in the chaos that ensues.
Initially believing she is the sole survivor, Dana soon learns that Marty, against the odds, is also alive. Together, they discover a secret elevator leading them deep into the lab, where they unveil a menagerie of terrors contained within cages. In a moment of clarity, Dana pieces together that the grotesque objects found in the cabin's cellar dictate which monsters can be unleashed upon them. In a climactic turn of events, the two release the horrors, leading to an unprecedented rampage that annihilates the lab staff, claiming Hadley’s life, while Dana inadvertently stabs Sitterson.
Venturing further, they encounter "The Director," who elucidates that global rituals of human sacrifice are performed annually to appease the Ancient Ones, brutal deities residing in the depths. The American ritual is particularly sinister, necessitating five specific archetypes to be sacrificed: the whore (Jules), the athlete (Curt), the scholar (Holden), the fool (Marty), and the virgin (Dana). To succeed, the hierarchy of death must be honored—whore first, virgin last. Amidst the turmoil, the Director implores Dana to eliminate Marty, as all other rituals have failed this year. The confrontation concludes chaotically as Dana fends off a werewolf attack, while Patience kills The Director, leaving Marty to dispatch all but Dana.
Choosing to defy the ruthless cycles of sacrifice, Dana and Marty share a joint in defiance of their fate. Suddenly, the temple floor splinters apart, and a colossal hand emerges from the abyss, obliterating both the facility and the cabin—a final testament to the horrors beyond comprehension.
