In 1997 Los Angeles is suffering from both a heat wave and a turf war between heavily-armed Colombian and Jamaican drug cartels. A Predator watches a shootout between the police and Colombians, observing as Lieutenant Michael Harrigan (Danny Glover) charges into the firefight to rescue two wounded officers and drive the Colombians back into their hideout. Before the police can follow them in, the Predator crashes through a skylight and kills the Colombians. Harrigan and his detectives Leona Cantrell (María Conchita Alonso) and Danny Archuleta (Rubén Blades) find the Colombians have been slaughtered. Harrigan pursues the gang leader onto the roof and shoots him, catching a glimpse of the camouflaged Predator's silhouette, but dismissing it as an effect of the heat. Harrigan is rebuked by his superiors for disobeying orders. He is also introduced to Special Agent Peter Keyes (Gary Busey), leader of a federal task force purportedly investigating the cartels, and Detective Jerry Lambert (Bill Paxton), the newest member of Harrigan's team.
The Predator then kills several Jamaican cartel members, who are murdering the Colombian drug lord Ramon Vega. Despite being ordered to wait for Keyes, Harrigan and his team enter the penthouse, where they find the Jamaicans' skinned corpses suspended from the rafters. Keyes kicks Harrigan's team out, but Danny later returns to continue investigating. He finds one of the Predator's speartip weapons in an air conditioning vent, but is then killed by the Predator. Harrigan vows to bring down Danny's killer, believing, they are dealing with an assassin. A forensic scientist finds the speartip does not correspond to any element on the periodic table. Harrigan meets with Jamaican drug lord King Willie (Calvin Lockhart), a voodoo practitioner, who tells him that the killer is supernatural. After Harrigan leaves, the Predator kills King Willie.
Cantrell and Lambert are intervening in a mugging on the subway, when the Predator attacks them. Cantrell herds the passengers to safety, while Lambert faces off against the Predator and is killed. The Predator is about to kill Cantrell as well, but releases her, when its thermal vision reveals, that she is pregnant. Harrigan chases the Predator, but is stopped by Keyes, who reveals that the killer is an extraterrestrial hunter with infrared vision, uses active camouflage and has been hunting humans for sport, citing the events of The Predator. Keyes and his team have set a trap in a nearby slaughterhouse, using thermally insulated suits and cryogenic weapons in an attempt to capture it for study. However, the Predator sees through the trap by using its mask to scan through various electromagnetic wavelengths and kills the team. Harrigan intervenes, shooting the Predator several times and removing its mask.
Still alive, the Predator kills Keyes using a throwing disc and escapes to the roof. Harrigan knocks it over the side and finds himself on a narrow ledge with the Predator hanging below. The Predator attempts to activate the self-destruct device on its forearm, but Harrigan uses the throwing disc to sever its forearm and destroy the device. The Predator falls through an apartment window and uses a medical kit to treat its wounds, then flees through the building. Harrigan follows it down an elevator shaft and finds its spacecraft in an underground chamber. Inside the ship, the two face off in a final duel, with Harrigan finally killing the Predator by impaling its chest with the throwing disc. A number of other Predators appear, collecting their dead comrade and presenting Harrigan with an antique flintlock pistol labeled "Raphael Adolini 1715". Harrigan escapes the ship, as it takes off and reaches the surface just as the remainder of Keyes' team arrives, furious that they were unable to capture the alien. Harrigan speculates, that the creatures will return.
- Danny Glover as Mike Harrigan
- Ruben Blades as Danny Archuleta
- Gary Busey as Peter Keyes
- Maria Conchita Alonso as Leona Cantrell
- Bill Paxton as Jerry Lambert
- Adam Baldwin as Garber
- Robert Davi as Captain Phil Heinemann
- Kent McCord as Captain B. Pilgrim
- Kevin Peter Hall as The Predator
- Teri Weigel as the columbian girl
- Morton Downey Jr. as Tony Pope
- Calvin Lockhart as King Willie
A novelization of the film written by Simon Hawke was released on December 1, 1990 by the publishing company Jove. The novelization provided a small amount of information regarding the fate of "Dutch" from the first film. Keyes recalls memories of speaking with the battered Major while infirmed in a hospital, suffering from radiation sickness. "Dutch" is said to have escaped from the hospital, never to be seen again. Furthermore, the novel tells a great deal of the story from the Predator's point of view, such as its humiliation of having its mask removed by Harrigan, and its reasoning for not killing Cantrell due to its discovery of her pregnancy.