Texas sheriff Edgar McGraw pulls up to a secluded liquor store in Texas known as Benny’s World of Liquor. After a brief interaction with the shopkeeper, he heads to the restroom. Inside, the notorious Gecko Brothers, Seth (George Clooney) and Richie (played by Quentin Tarantino), appear with hostages in a tense standoff that has surely escalated. Seth menaces the shopkeeper, insisting he remain calm. Just moments later, the sheriff returns to the store, only to have his life abruptly taken by Richie’s ruthless shot to the head.

Richie, in his impulsive nature, argues with Seth, claiming the shopkeeper had signaled for help. As chaos ensues, the shopkeeper tries to defend himself, leading to a gunfight. In a final, desperate act, Seth ignites a roll of toilet paper dipped in lighter fluid, incinerating the shopkeeper before they make their harrowing escape amid the explosion that engulfs the liquor store. Seth furiously scolds Richie for turning their already precarious situation into a catastrophic mess, all when a clean getaway was possible.

The two brothers then drive along the highway while an ominous x-ray shot into their trunk reveals another hostage bound and gagged. At a motel, they hatch their escape plan to flee to Mexico and rendezvous with Seth’s ally, Carlos (played by Cheech Marin). A news report on their heinous acts flashes on the screen, foreshadowing the consequences of their depravity. When Seth returns to find that Richie has committed further crimes against their hostage, he chastises Richie for his insanity, acknowledging their desperate need for new hostages.

Their next targets are Pastor Jake Fuller (Harvey Keitel) and his family—his teenage daughter Kate (Juliette Lewis) and adopted son Scott (Ernest Liu). After abducting this family, the brothers hijack their RV, forcing them violently toward the Mexican border. A tense moment occurs when they are stopped by a customs agent played by Carlos. Inside, Richie experiences a disturbing fantasy involving Kate, but before things escalate, Seth intervenes, knocking out Richie just in time to keep their cover intact. With a silver tongue, Jake pacifies the customs officials, enabling them to cross into Mexico unharmed.

Once in Mexico, Seth declares they will spare the hostages’ lives for their compliance during the border check. He orders Jake to drive to an eccentric bar known as The Titty Twister, hidden deep in the desert. Outside, tension builds as Seth confronts the bouncer, leading to a physical scuffle before they are allowed inside. After unwinding with drinks and witnessing a sultry performance by Santanico Pandemonium (Salma Hayek), the atmosphere turns sinister when Richie, in his unpredictable manner, escalates matters further, resulting in a chaotic and violent confrontation.

Amidst the carnage, Santanico suddenly reveals her true form as a vicious vampire, attacking Richie who succumbs to his tragic fate soon after. The bar’s patrons, along with its staff, transform into horrific creatures, leading to a ferocious battle for survival. As Seth grapples with the grief of losing his brother, he witnesses Richie’s transformation into a vampire and makes the heart-wrenching decision to eliminate him.

In a desperate attempt to endure, Seth retreats into alcohol as the remaining survivors band together to fight off the vampire swarm. Tensions rise when a transformed Sex Machine (Tom Savini) begins his rampage, biting those around him, igniting a succession of deadly encounters. Fueled by a desire to protect the children, Jake urges his kids to promise that if he too becomes a creature of the night, they will be the ones to end his existence.

The battle intensifies, leaving only Seth and Kate standing amidst the chaos. Just as the situation seems hopeless, sunlight pierces the darkness, causing havoc among the remaining vampires. In a twist of fate, Carlos breaks through to provide a much-needed escape route. The radiant light triggers a calamity, resulting in an explosion that eradicates the vampire threat but not without great losses.

In the aftermath, Seth finds Carlos and unleashes his fury about the horrors they faced, blaming him for bringing them to the ill-fated bar. As negotiations unfold regarding their future, Seth hands Kate wads of cash and instructs her to return home. As he drives away from the ruins of the bar, the camera pans out, revealing that beneath the destruction lies an ancient Aztec ziggurat, hinting at the dark forces at play.