Following the events of Alien vs. Predator, a Predator ship is leaving Earth carrying Alien facehuggers, and the body of Scar, the Predator that defeated the Alien Queen. A chestburster erupts from Scar's body; it is a new creature that is a hybrid of both species. It quickly matures into an adult Predalien, makes its way onto a scout ship that is then detached from the Mothership, and starts killing all the Predators on the ship. A Predator's weapon fire punctures the hull and the scout ship crashes in the forest outside of Gunnison, Colorado.
With the Predators dead, the Predalien and several facehuggers escape, implanting embryos into a nearby father (Kurt Max Runte) and son (Liam James) and several homeless people living in the sewers. An injured Predator sends a distress signal before being killed by the Predalien. The distress signal reaches the Predator home world and a lone Predator, Wolf (Ian Whyte), responds, travels to Earth to track and kill the Aliens. He begins to erase the evidence of the Aliens' presence by destroying the crashed ship and using a blue liquid to dissolve the bodies of the facehuggers and their victims.
Meanwhile, ex-convict Dallas Howard (Steven Pasquale) has just returned to Gunnison after serving time in prison. He is greeted by Sheriff Eddie Morales (John Ortiz) and reunites with his younger brother Ricky (Johnny Lewis). Ricky has a romantic interest in his classmate Jesse (Kristen Hager) and is constantly harassed by her boyfriend Dale (David Paetkau) and two of his friends. Kelly O'Brien (Reiko Aylesworth) has also just returned to Gunnison after serving in the military, and reunites with her husband Tim (Sam Trammell) and daughter Molly (Ariel Gade).
Wolf fights a number of Aliens in the sewers, and as the battle reaches the surface several of them disperse into the town. Wolf pursues some to the power plant, where collateral damage from its weapons causes a city-wide power outage. Ricky and Jesse meet at the high school swimming pool but are interrupted by Dale and his cohorts just as the power fails and an Alien enters the building, killing Dale's friends. Another Alien invades the O'Brien home, killing Tim while Kelly escapes with Molly.
Kelly, Molly, Ricky, Jesse, Dale, Dallas, and Sheriff Morales meet at a sporting goods store to gather weapons. Troops from the Colorado Army National Guard arrive but are quickly killed by the Aliens. When the battle between Wolf and the Aliens enters the store, Dale is killed and Wolf's shoulder cannons are damaged; he is able to modify one into a hand-held blaster.
As the survivors attempt to escape Gunnison, they make radio contact with Colonel Stevens (Robert Joy) and learn that an air evacuation is being staged at the center of town. Kelly is suspicious of the military's intentions, and convinces a small group to go to the hospital where they hope to escape by helicopter, while Sheriff Morales heads to the evacuation area with the rest of the surviving citizens. The hospital, however, has been invaded and overrun by the Aliens and the Predalien, who has impregnated some pregnant women to breed more Aliens. Wolf soon arrives and in the ensuing battle, Jesse is killed, Ricky is injured by the Predalien, and Dallas takes possession of Wolf's blaster cannon after the Predator is attacked by an Alien and both tumble down an elevator shaft.
As the battle reaches the rooftop, Dallas, Ricky, Kelly, and Molly escape in the helicopter while Wolf, having survived the fall, battles the Predalien in hand-to-hand combat. Wolf and the Predalien mortally wound each other just as a military jet arrives. Rather than a rescue airlift, it is an F-22 Raptor, executing a tactical nuclear strike with a B83 nuclear bomb that destroys the entire city, killing all the extraterrestrials (including Wolf and the Predalien) along with the remaining citizens. The shock wave causes the fleeing helicopter to crash in a clearing, where the survivors are rescued by the military. Wolf's blaster cannon is confiscated, and Colonel Stevens presents it to Ms. Yutani (Francoise Yip). Ms. Yutani tells Colonel Stevens that the world is not yet ready for this kind of advanced technology. Colonel Stevens replies, "But this isn't for our world, is it, Ms. Yutani?"
Who does Wolf fight in the sewers?
Aliens