FBI agent Neville Flynn is escorting a key witness on a flight from Hawaii to Los Angeles to testify against a powerful mob boss. The safety of their flight is compromised when the mob boss orchestrates an assassination attempt in an unusual and deadly manner: releasing a crate full of venomous snakes during the flight as a bid to eliminate the witness. The snakes are set free in the cargo hold, but soon find their way throughout the plane, causing panic and chaos among the passengers and crew.

Amidst the terror, Agent Flynn takes charge, determined to protect his witness and keep the passengers safe. With the help of the cabin crew, including a resourceful flight attendant, and other brave passengers, Flynn strategizes to control the snake threat. They face numerous challenges, including figuring out how to keep the snakes away from the passengers and navigating the plane with the pilot incapacitated. The situation escalates as the snakes continue to spread through the aircraft, forcing Flynn and the passengers to confront their fears and work together to survive the perilous journey.