The story centers around Nathaniel Nucci, who leaves the military when his wife becomes pregnant hoping to lead a "normal" life. All is well for 13 years until his wife and child are part of collateral damage on a botched Mafia hit. Blinded by rage, Nathaniel infiltrates the Mafia organization responsible for the murder of his family. He ultimately becomes a contract killer for the head of one of Philadelphia's largest Mafia families, while keeping his identity hidden.

When Kyle, a pimp in love with Juliet, and Trevor, her wanna-be mob-affiliated boyfriend, find themselves in dire straits, they devise a plan to kidnap Romeo, a wealthy movie producer who is infatuated with Juliet.

A young couple's world is shattered when their child goes missing in broad daylight. Shortly after, another child mysteriously disappears from school. When the parents get no help from the police or the school, they band together to take matters into their own hands.

Following the events of Sacrum Vindictae II, Nathaniel Nucci is on the run. Facing insurmountable odds, Nucci must confront his past, his mistakes, and his own mortality.