In Guesta Verde University, the deranged Professor Curien is trying to bring back the dead, killing students for the experiment. There is an outbreak of zombies in the campus, and the government sends a NSA medical research team, formed by Dr. Alexandra Morgan a.k.a. Nightingale and lieutenant Ellis, with a special force leaded by lieutenant Dalton, trying to get the zero sample from the first generation zombie. The team has a very short time to accomplish their mission and leave the place before missiles are sent to destroy the area. However, the place is crowded of hyper sapiens and the group has to fight to survive.

Set on an island off the coast, a techno rave party attracts a diverse group of college coeds and a Coast Guard officer. Soon, they discover that their X-laced escapades are to be interrupted by zombies and monsters that attack them on the ground, from the air, and in the sea, ruled by an evil entity in the House of the Dead... Prequel to the House of the Dead video games.