Cuando una nave exploradora Predator se estrella, aparece en un pueblo de Colorado. Los Aliens a bordo escapan y matan a todos los Predators excepto a uno. El último Predator superviviente debe ahora acabar con todos los Aliens, así como con el terrorífico Pred-Alien que fue engendrado en la anterior entrega. Mientras tanto, los habitantes del pueblo están siendo inutilmente atrapados en medio del último enfrentamiento entre estas dos criaturas míticas.

A little town in the hills of Colorado will become the battleground between two of the deadliest extra-terrestrial lifeforms - the Alien and the Predator. When a Predator scout ship crash-lands in the hills outside the town, Alien facehuggers are released in the crash, and an even more evil creature - a hybrid Alien/Predator - is also released. A man & his son hunting in the forests near the crash site soon become the first victims of the facehuggers, and when a Predator receives data about the crash on his home planet, he comes to Earth. One at a time, the inhabitants of the town become targets of the Aliens and the Predator, including the local sheriff, a young female soldier recently returned from Iraq, and several teens. Though the National Guard is called in, they are unable to stop the deadly creatures, and a plan is set in motion to destroy the town with a nuclear device...