Ray Tango and Gabriel Cash are narcotics detectives who, while both being extremely successful, can't stand each other. Crime Lord Yves Perret, furious at the loss of income that Tango and Cash have caused him, frames the two for murder. Caught with the murder weapon on the scene of the crime, the two have no alibi. Thrown into prison with most of the criminals they helped convict, it appears that they are going to have to trust each other if they are to clear their names and catch the evil Perret.
A hardened New Orleans cop, Dave Robicheaux, finally tosses in the badge and settles into life on the bayou with his wife. But a bizarre plane crash draws him back into the fray when his family is viciously threatened.