The film follows a man, Jack (Jesse Metcalfe), faking insanity in order to save his sister, Lily (Kiele Sanchez), who has been involuntarily institutionalized. The siblings soon find that the strange doctor at the asylum, Mr. Gianetti (Peter Stormare), has been testing an experimental compound, orphium, on the patients that seems to be turning them into flesh-eating zombies; Loomis (Kurt Caceres), another patient, spreads the infection. The two siblings band together with a terminally paranoid man, Dave (Kevin Sussman), and a helpful nurse, Nancy (Olivia Munn), in the hopes of finding a way out of the asylum. They are attacked by most of the prisoners and staff, who kill Nancy; while on the 4th floor, they encounter the doctor, who gives Dave an icepick lobotomy, incapacitating him; he attempts to get Jack too, but ends up being infected by Loomis. At the end of the film, as the two siblings are in a police car heading to the asylum to investigate, the officers (Mark Kelly & Sharon Schaffer) accidentally let the patients escape into the outside world. It ends with a panning shot, revealing the city below the asylum's hillside location. The secondary plot focuses on the affair between Charles (Evan Parke) and Heather (Lisa Athrowe).

Former superhero Jack Shepard, (also known as Captain Zoom), is called back to work to transform an unlikely group of ragtag kids into a new generation of superheroes at a privacy Academy and save the world from certain destruction. The project holds an audition of would-be members, most of whom possess useless or disgusting powers. In the end, Dylan, a 17-year-old boy who can turn invisible Summer, a 16-year-old girl with telekinetic powers Tucker, a 12-year-old boy with the power to enlarge any part of his body Cindy, a 6-year-old girl with super strength.

A mysterious killer video tape is circulating around. One look at this tape and you have seven days left to live. News Reporter Cindy Campbell (Faris) witnesses this video tape and tries to work out a way to prevent her death. But this is not the only mystery to appear. Crop circles have been appearing in the local farm of Tom (Sheen) and George (Rex). With help from Aunt Shaneequa (Latifah), Cindy suspects that the aliens may be linked with the killer tape and must now work out both mysteries before it's the end of the world.