Following the harrowing events that transpired in Alien vs. Predator, a Predator ship departs from Earth, carrying with it Alien face-huggers and the remains of Scar, a Predator who bravely defeated the Alien Queen. However, the situation takes a dark turn when a Chest-Burster emerges from Scar's body, evolving into a terrifying hybrid creature known as the Predalien. This formidable entity swiftly ages into adulthood and begins a gruesome spree, mercilessly eliminating all Predators aboard the scout ship. As the Predators unleash their plasma casters in a desperate attempt to defend themselves, damage to the ship's hull becomes inevitable, culminating in a catastrophic crash in the tranquil forests surrounding Gunnison, Colorado.
With the Predators now extinct, the Predalien along with several face-huggers manage to escape their confines, violently implanting embryos into nearby unsuspecting victims, including a Father Buddy Benson (portrayed by Kurt Max Runte) and his son Sam (played by Liam James), as well as a group of unfortunate homeless individuals lurking in the sewers. In a final stand against the surge of chaos, an injured Predator sends out a distress signal before meeting its demise at the hands of the relentless Predalien. This cry for help reaches the distant home world of the Predators, stirring Wolf (brought to life by Ian Whyte), a solitary and determined Predator who promptly makes his way to Earth with the singular mission of annihilating the Alien threat. Upon reviewing distressing footage captured onboard the Predator ship, he identifies the deadly hybrid creature wreaking havoc among his kind.
Upon his arrival at the crash site, Wolf meticulously investigates the wreckage, confirming his worst fears: the Aliens have indeed fled the wreckage. Quick to react, he confiscates weapons from the slain Predator and embarks on a mission to conceal any trace of the horrific Aliens, employing a mysterious blue liquid to dissolve the corpses of both the face-huggers and their unfortunate hosts. Meanwhile, ex-convict Dallas Howard (played by Steven Pasquale) returns to Gunnison after serving his prison sentence, where he joyously reunites with Sheriff Eddie Morales (John Ortiz) and his younger brother Ricky (Johnny Lewis).
Ricky, who is infatuated with Jesse (Kristen Hager), finds himself in a heated confrontation with her aggressive boyfriend Dale (David Paetkau). During a pizza delivery, tempers flare as Ricky and Dale engage in a fierce verbal dispute; this escalates into violence when Dale tosses Ricky's keys into the depths of the sewer system. In a moment of brotherly concern, Dallas intervenes, guiding Ricky into the sewers to retrieve his keys. What ensues is an eerie encounter with unsettling sounds and unfamiliar creatures lurking beneath the surface, prompting them to swiftly retreat.
Simultaneously, Kelly O'Brien (portrayed by Reiko Aylesworth) also returns to her hometown of Gunnison after completing her service in the military, reuniting with her husband Tim (Sam Trammell) and their daughter Molly (Ariel Gade). The tranquil atmosphere of town is shattered when Buddy and Sam are reported missing. Deputy Ray Adams (Chris William Martin) bravely ventures into the woods to locate them but instead becomes prey to the lurking Predalien. Desperate for information, Ray's wife Carrie (Gina Holden), a pregnant waitress, voices her concerns to Eddie, as Ray has always been good about calling home during troubling times. Eddie investigates the woods, only to discover Ray gruesomely hung upside down, skinned alive.
In the midst of this chaos, Jesse invites Ricky to go swimming later that evening at the local pool, revealing that she has ended her tumultuous relationship with Dale. Just as they rendezvous at the pool, a catastrophic power failure coincides with an Alien's entrance into the building, spellbindingly horrid carnage ensues, converting Dale's friends into helpless victims. Meanwhile, another Alien infiltrates the O'Brien residence, resulting in Tim's tragic demise while Kelly and Molly barely escape.
As panic escalates, the disparate group of survivors, including Kelly, Molly, Ricky, Jesse, Dale, Dallas, and Sheriff Morales convene at a sporting goods store, arming themselves to fend off the impending doom. Just as military forces from the Colorado Army National Guard arrive, they are swiftly dispatched by the ever-growing Alien threat. The chaotic skirmish intensifies, leading to Dale's brutal death at the hands of the extraterrestrial menace, while Wolf manages to modify one of his damaged shoulder cannons into a makeshift hand-held blaster.
Amidst their frantic attempts to escape Gunnison, the group manages to make contact with Colonel Stevens (Robert Joy), who informs them of a military air evacuation being staged in the town's center. Kelly remains skeptical of the military's true intentions and persuades a small group to traverse to the hospital, hoping to evade danger via helicopter, while Sheriff Morales leads a larger faction toward the evacuation site. Their hopes rapidly dissipate as they discover that the hospital has succumbed to an even more dreadful takeover by Aliens and the Predalien, who has already begun to breed within its walls.
As Wolf arrives on the scene, a fierce battle erupts. In the midst of the chaos, Jesse is slain, Ricky suffers grievous injuries from the Predalien, and in an unfortunate twist, Dallas seizes Wolf's blaster cannon just before an Alien attacks, resulting in both being sent plummeting down an elevator shaft. As the fight reaches a climactic showdown on the hospital rooftop, Dallas, Ricky, Kelly, and Molly make their daring escape via helicopter, while Wolf, having survived the fall, faces off against the formidable Predalien in a brutal clash.
In a surreal twist of fate, both Wolf and the Predalien inflict life-threatening injuries upon each other just as military jets swoop in with malevolent intent. Rather than orchestrating a rescue, an F-22 Raptor aims its sights on the town and executes a tactical nuclear strike, enveloping Gunnison in catastrophic destruction, obliterating all Aliens alongside the remaining innocent citizens. The shockwave from the blast sends the fleeing helicopter spiraling downwards into a clearing, where the fortunate survivors are ultimately rescued by the military.
In the aftermath, Colonel Stevens confiscates Wolf's plasma pistol from Dallas, who receives medical attention alongside his brother. A glimmer of hope arises when Molly is reassured by her mother that the nightmare has come to an end, and the monsters have been vanquished. Finally, Colonel Stevens presents the plasma pistol to Ms. Yutani (Francoise Yip), who, with a grave expression, indicates that the world is not yet prepared for such advanced technology. Colonel Stevens responds, > "But this isn't for our world, is it, Ms. Yutani?"
