The life of Griselda Blanco, a pioneer in the Miami-based cocaine trade, unfolds as she makes her way to the U.S. at 17 with a fake passport and her first husband Carlos. In Queens, she becomes enticed by the lucrative drug world and quickly gets involved with local runners. Griselda's cunning plan utilizes vulnerable individuals, including women, the elderly, and children, as mules, and she creates fake-bottom suitcases to smuggle cocaine from Colombia. As wealth pours in, her sons abandon school to join the family business.

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