In Manhattan, cockroaches are spreading the deadly "Strickler's disease" that is claiming hundreds of the city's children. Dr. Peter Mann, Deputy Director of the Centers for Disease Control and Prevention, recruits entomology Dr. Susan Tyler, who uses genetic engineering to create what she calls the Judas breed, a large insect that releases an enzyme which accelerates the roaches' metabolism and causes them to starve to death faster than they can take in nourishment. The disease is successfully eradicated, and Peter and Susan later marry.
Four years after the events of the first film, after three men are discovered hideously mutilated (their faces have been removed) and strung up among New York City's high-tension wires, Detective Klaski (Bruno Campos) stumbles upon a link: Each of the men knew entomologist Remy (Alix Koromzay), a teacher at an inner-city high school. Klaski considers Remy to be a prime, albeit unlikely, suspect in the killings until he witnesses for himself the shape-shifting creature that has been stalking Remy: an intelligent mutant insect with the face of its previous victim. It wants to mate with Remy. Klaski, Remy and a pair of her students get trapped inside the school as the creature hunts them down.Remy gets separated and runs into the creature who does not harm her but seems interested.Remy then gets cornered and the creature attempt to give her pizza. Meanwhile, a special forces unit, headed by the militant leader known only as Darksuit (Edward Albert), gets ready to fumigate the school with poisonous gas.