Espionage, crime and politics collide in modern day Mexico City. A brilliant but self-destructive CIA officer, his young and ambitious Mexican-American protegee, and the city's inspirational but secretive Mayor all struggle for power during an invasion of the city by the world's most murderous drug cartel.

Wayne works with the joint Mexican-American "Fusion Center” to track the sicarios responsible for the recent bloodshed. Isa ignores orders to stay in the embassy and instead pursues a lead to the Guerrero Cartel. And Lalo puts his career at risk, battling the Mexican President for control of the narco investigations.