Santa Diabla is the story of Santa Martínez, a woman who seeks revenge for the murder of her husband Willy Delgado. Santa's revenge includes marrying Humberto Cano, a powerful attorney in Marrero. Humberto hired Willy Delgado to give piano lessons to Humberto's niece Daniela Milan at the Cano family's home, until Bárbara Cano, Daniela's mother and Humberto's sister, accused Willy of harassment and attempted rape of her daughter. Blaming the Canos for the unjust death of her husband, Santa intends to destroy the Cano family, but as she tries to complete her mission, she meets and falls in love with Santiago Cano, Humberto and Bárbara's brother. All the while Inés Robledo who is a rich and evil woman uses her power and influence to try and keep Santiago and Santa apart because of her obsession with Santiago.