Bill Marks is a Federal Air Marshall for whom every day is the same until this one. On this plane ride, he starts receiving text messages from someone claiming to be on the flight and threatening to kill passengers. In a race against the clock, he must identify and stop the killer to save everyone on board.

On a flight transporting dangerous convicts, murderer Ryan Weaver manages to break free and cause complete chaos throughout the plane. As various people on board fall victim to Weaver, it is ultimately down to flight attendant Teri Halloran to keep the aircraft from crashing, with on-ground support from an air traffic controller. While Halloran struggles to pilot the plane, Weaver continues to terrorize the surviving members of the crew.

The co-pilot and engineer of a passenger jet struggle to keep the plane airborne after a marshal onboard, transporting a murderer to prison, has a heart attack and the killer uses his gun to shoot the captain and blow out the hydraulics.

While on a flight home from Colombia, the plane that Dr. Carrie Ross and her daughter are on is attacked by bullet ants whose sting is the most painful and deadliest on the planet. Joining forces with air marshal Ethan Hart, Dr. Ross, an entomologist, tries desperately to save the flight from disaster. In the end, their struggle brings them closer together and offers the couple hope for the future.