Two masked wrestlers, Boa and Python, grapple in Atlantic City, New Jersey. Enjoying this spectacle are Broddick Adamo Palladino, a multi-millionaire casino owner, and his girlfriend Eve Angel Boris Reed. Their night takes an unexpected turn when a phone call arrives: Ramon Assen Blatechki informs Broddick in York, Pennsylvania that his “package” has arrived overseas from South America and is being delivered. Broddick, delighted, promises Ramon a lucrative reward for his work.
During the convoy ride, the contents in the back awaken and grow enraged. Ramon halts the group, arms a tranquilizer gun, and orders a panel to be opened. A serpentine tail bursts through, causing chaos. A guard fires wildly, striking the main control circuit on the back of the truck. The sealed container’s door swings open, revealing an immense, nightmarish reticulated python—roughly 80 feet (24 meters) long and weighing about 12 tons. It tears through the vehicle, slaughtering the men as Ramon detonates a bomb to destroy the convoy, but the monstrous snake survives the blast.
Broddick’s plan becomes clear: bring extreme big-game hunting to the city as another entertainment for the ultra-wealthy, and the python is to be the prize. After a news report confirms the convoy’s destruction, Broddick realizes the snake has escaped and moves to assemble his hunting entourage to pursue it.
Forty minutes outside Philadelphia, FBI Agent Alan Sharpe [Kirk B.R. Woller] investigates the wreck and finds a large snake scale among the debris. Aware of the broader events surrounding the python, Sharpe is determined to stop further bloodshed. He enlists herpetologist Dr. Steven Emmett [David Hewlett] and marine biologist Monica Bonds [Jaime Bergman] to devise a plan. They propose merging Monica’s dolphin-camera headgear and tracking system with Emmett’s engineered giant Scarlet Boa named Betty, a 70-foot-long (21 m), 11.5-ton predator, in hopes that Betty will locate and kill the python.
With a backup team of FBI agents and US Army soldiers, the trio transports Betty to a water-treatment facility. She quickly enters the facility and begins tracking the python, though the system delivers only sporadic coverage. Broddick and his remaining hunters reach the opposite end of the facility and begin their pursuit, stumbling upon a nest of eggs guarded by Betty, whom they did not anticipate. Betty constricts Eve, killing her, a blow that pushes Broddick into a furious resolve. He escapes, while his team is dispatched by both snakes. Sharpe is accidentally killed in the crossfire.
Broddick is captured, and the tracking system comes back online. Dr. Emmett finally detects Betty’s nest and resolves to return to the treatment facility to protect it, with Monica choosing to accompany him. Broddick, however, has slipped away and commandeered an APC. Following the tracking signals, Emmett and Monica close in on Betty, locating her nest at a nightclub. Betty bursts through the floor, and the two snakes—Betty and the python—engage in a brutal struggle beneath the disco lights. They seize Broddick in a violent tug-of-war, each consuming half of him.
The battle continues beneath the disco and then spills onto subway tracks. A speeding train looms, and Emmett activates an electrical spike device implanted in Betty’s head, stunning her and sending the python off the rails just as the train slams into them, decapitating the python. Though they celebrate, Emmett and Monica soon discover Betty has crawled away. They return to the treatment facility to bring Betty and her remaining eggs home, hoping to safeguard the creatures from further harm and preserve the nest.