Jay Baruchel travels to Los Angeles to reconnect with his old friend, Seth Rogen, who invites him to a lively housewarming party thrown by James Franco. Amidst the chaos of the celebrations—where [Rihanna] slaps [Michael Cera] for a cheeky gesture and [Mindy Kaling] has her sights set on Cera—Jay feels increasingly out of place. Seeking solace, Seth and Jay head to a nearby convenience store, only for their excursion to be interrupted by mysterious blue beams of light that begin to abduct partygoers from the street. When they return to Franco's house, they find the party miraculously intact but no one believes Jay's wild tale of the chaos, especially Seth, who was pinned under a steel cart during the incident.
As the night unfolds, an earthquake rattles the building, sending the panicked guests outside to witness Hollywood Hills engulfed in flames. Chaos ensues as [Michael Cera], inebriated and high, meets a comically tragic fate when a sinkhole opens up beneath him, dragging along [Rihanna], [Mindy Kaling], [Jason Segel], [Christopher Mintz-Plasse], and [Martin Starr]. A mishap with [Jonah Hill] leads to Jay falling into the same pit, but luck allows him to manage a narrow escape back to the safety of the house, where he reunites with Seth, James, Craig Robinson, and others busy grappling with the scene.
While the group begins to inventory their supplies and formulate a survival strategy, they joke about how actors are the first to be rescued in emergencies. That night, Seth speculates that if there were indeed blue lights collecting souls, they might not be virtuous enough to enter heaven, as Jay fears it's a sign of the Apocalypse.
The next day, the crew's dwindling supplies complicate matters further when [Danny McBride], a latecomer to the party, wakes up and carelessly uses their food and water. Skepticism mounts as a decapitated head, resulting from a nearby attack, crashes into their living room, spreading chaos and blood. The mood shifts dramatically as Jay's warnings of potential doomsday become a source of tension among the friends, notably when [Emma Watson] returns, claiming she survived by hiding in a drainpipe for days, yet misinterprets their discussions as plots for assault.
With tempers flaring, a desperate encounter pushes Jay and Seth to consider the implications of Craig's horrifying encounter in the basement and Jay's earlier apocalyptic theories. All while Danny's selfish behavior continues to erode group morale. Throughout the night, battles with demons begin as [Jonah Hill]'s possession wreaks havoc, leading to an explosive confrontation that ends with a catastrophic fire in the house.
With it becoming increasingly clear that they must escape to survive, they decide to flee to James' Malibu home, only to be met with a demonic guardian of the vehicle. In a moment of selflessness, Craig sacrifices himself and is Raptured to safety, triggering realization among the others that noble gestures may grant them salvation.
On their journey, they cross paths with a band of cannibals led by Danny, where James makes the ultimate sacrifice—only to find himself devoured when he insults the leader. Amidst the madness, Jay and Seth face off against Satan himself, leading to a heartfelt apology from Jay that aids his ultimate ascension to Heaven, which heaps irony upon their wild adventure as Seth remains behind.
The climax culminates in a fantastical reunion in the afterlife, where every wish is granted, including a surprise performance by the Backstreet Boys, as Jay experiences an absurd moment of joy where everyone dances along to "Everybody (Backstreet's Back)"—all in the realm of heavenly bliss.
