A group of National Guard trainees find themselves battling against a vicious group of mutants on their last day of training in the desert.
The movie opens in the New Mexico desert, with the mutants from the first film having captured a woman who is being forced to breed mutant children. As soon as she has given birth, Papa Hades (Michael Bailey Smith) kills her as the baby she unwillingly gave birth to dies. Nearby, a group of scientists working in the desert hills are attacked by Letch (Jason Oettle). It is also hinted at the beginning of the film that the surviving members of the Carter family from the first film were not killed by Papa Hades' mutant clan and managed to escape the hills.
Some time later, a group of National Guard reservists in training are sent into the hills to resupply the scientists, who are working for the Department of Defense on installing a surveillance system (implied to be a result of the events in the first film). The soldiers arrive to find the camp apparently abandoned, with no sign of their commanding officer or any of the civilians, with outside radio contact impossible due to the topography. When the radio operator, Spitter (Eric Edelstein), picks up a faint distress call, the sergeant (Flex Alexander) organizes a rescue mission, leaving behind Napoleon (Michael McMillian) and Amber (Jessica Stroup).
The search party discovers the mutilated body of a scientist in the hills, while Amber and Napoleon pull another mutilated and dying scientist from beneath the portable toilet. On her way to join the group, Amber is attacked by Stabber (Tyrell Kemlo), but a returning (and injured) Mickey (Reshad Strik) drives him off. Just as Napoleon catches up, Mickey is pulled into a bolt-hole and killed. At the same time, the remaining troops are also attacked by Letch, leading to the sergeant accidentally being killed by Spitter's friendly fire. Spitter himself is later killed by an unseen mutant sabotaging his rappelling gear.
The troop soon locates their commanding officer, who has clearly become unhinged from recent events. He warns them of the mutants' plans to capture women for breeding and kill everyone else, committing suicide upon being asked how to escape the hills. With their remaining gear stolen, the team are forced to try to find another way down the mountain. In the process, Missy (Daniella Alonso) is captured and taken into the tunnels by Chameleon (Derek Mears) who attempts to rape her but is interrupted by Papa Hades who stops him, but then savagely rapes Missy himself for the purpose of impregnating her despite her pleas for help, while the remaining troops chase after her. They manage to kill mutants Chameleon and Grabber (Gaspar Szabo), but Stump (Ben Crowley) and Delmar (Lee Thompson Young) are also killed while underground. Crank (Jacob Vargas) is also killed via a trapped crate of dynamite that he attempts to take with him, incidentally triggering the explosion.
While in the mines, the troop locate a non-violent mutant named Hansel (David Reynolds) who eventually shows them the way out of the mines, but Amber insists on returning to find Missy. They find and free her, then having to fight Papa Hades, whom they manage to kill. The final three National Guard troops—Amber, Napoleon, and Missy—make their way out of the mine alive.
Epilogue text appears in the closing scene, revealing the dead troops to have been listed as "absent without leave" (although there is no mention of whether or not Missy became pregnant as the result of Papa's rape). At least one mutant is seen alive, and making use of the high-tech surveillance equipment to watch the survivors as they leave the mine. One mutant shown to be frustrated that the survivors got away.