Cocaine Cowboys 2 follows the life of Charles Cosby as he goes from a small-time drug dealer to the head of a major empire in Oakland, California, in 1992. Cosby acts as the narrator though most of the film as he documents his business and personal relationship with the head of the Medellin Cartel, Grisedela Blanco.
Charles Cosby has his life turn upside down after he sends a love letter to Griselda Blanco while she was serving time in a California prison on drug charges. Blanco was famously known for operating a ruthless cocaine empire in Miami in the 1980s before getting arrested. She starts a new drug empire from prison with the help of her new lover. The partnership turns Cosby into a millionaire within a matter of months, but the entire empire soon falls apart when Blanco is unable to control her urge to commit violent crimes.