Several years after the small desert town of Perfection, Nevada, battled subterranean creatures known as Graboids, Earl Bassett has resigned himself to ostrich farming, leaving behind his days of hunting the lethal predators. However, Earl's quiet life is disrupted when he is approached by Grady Hoover, an enthusiastic fan, and Carlos Ortega, a wealthy businessman who reveals that the Graboids have reappeared in an oil field in Mexico and are killing workers. Ortega extends a lucrative offer to Earl to help hunt down and exterminate the creatures. Despite initial hesitance, the temptation of earning a hefty bounty for each Graboid killed prompts Earl to team up with Grady and head south of the border.

Upon arrival in Mexico, Earl and Grady gear up for what seems like a straightforward task until their initial successes are marred by an unexpected development: the Graboids have evolved into a new phase of their life cycle, giving rise to surface-dwelling creatures known as Shriekers. The situation rapidly escalates, compounded by the creatures' mysterious ability to multiply quickly. The duo's mission becomes more perilous as they, along with geologist Kate Reilly, must adapt their strategy and fight for survival against this new rapidly growing threat.