The movie kicks off with Tango, portrayed by Sylvester Stallone, driving a sleek late-model Cadillac convertible in pursuit of a suspicious tanker truck. Dressed sharply in a three-piece suit with impeccably styled hair, he cleverly halts the truck. When the authorities from LA County investigate, they discover nothing but gasoline in the tank. In a surprising twist, Tango shoots the tank, and a torrent of cocaine spills out of the bullet hole.
Simultaneously, we are introduced to Cash, played by Kurt Russell, who arrives at his apartment in an old Corvette. His long, shaggy hair and casual attire of jeans and a T-shirt contrast sharply with Tango's polished look. However, Cash faces trouble when he is shot by an intruder. Thanks to his bullet-proof vest, he survives and later chases down the assailant in a thrilling parking garage confrontation. At the police station, he forces the shooter to divulge details of a deal planned for that night.
Unbeknownst to them, a devious plot orchestrated by Perret is underway to frame both Tango and Cash for murder. The detectives find themselves in an empty building, where they encounter Requin, played by Brion James, who is working for Perret. After an unexpected meeting and a grim discovery of a murdered man with hidden audio equipment, they find themselves swarmed by FBI agents. Wyler, the agent in charge, finds Cash's gun on the scene, resulting in both detectives being arrested.
During their trial, Requin sets them up further with an audio tape that appears to capture them discussing a drug deal and leads to their conviction. They plead "no contest" to lesser charges, which sees them sentenced to a minimum-security prison. Unfortunately, they are instead sent to a maximum-security facility teeming with former adversaries. Within the prison walls, they endure torment from Perret, Requin, and other inmates until help arrives from Matt Sokowski, the assistant warden, who proposes an escape plan. Yet, Tango is reluctant to accept the offer. When Cash attempts to flee, he discovers Sokowski's lifeless body, leading to an intense struggle with the other prisoners. Tango comes to his rescue, and together they make a daring escape.
Once outside, Tango tells Cash to visit his sister Katherine, played by Teri Hatcher, if he needs assistance. They then embark on a mission to confront the witnesses who wrongly testified against them. Their investigation reveals that Requin orchestrated the scheme, and Cash learns that the incriminating tape was fabricated by the audio expert. Cash finds Katherine working as an exotic dancer at a nightclub and later reunites with Tango, who meets with his commanding officer. They obtain Requin's whereabouts and realize they have just 24 hours to uncover who is pulling the strings.
Tango and Cash set out to capture Requin, successfully extracting Perret's name from him. Armed with an advanced assault vehicle, they charge into Perret’s headquarters, demolishing everything in their path, including armed trucks and guards. Tension escalates as Perret kidnaps Katherine, initiating a countdown for the building's self-destruct sequence. After a fierce showdown with Requin and another henchman, Tango and Cash emerge victorious. They face Perret, who threatens Katherine, but the detectives eliminate him, escaping just as the building detonates.
As the dust settles, Tango and Cash share a lighthearted banter regarding Cash's romantic interest in Katherine. The film concludes with a triumphant newspaper headline proclaiming their exoneration, sealing their victory over the forces that sought to bring them down.
