Nino Santangelo is an influential Cuban heroin dealer. After Lincoln Clay kills Sal Marcano's second capo, Marcano is in need of money, so he agrees to let Santangelo sell drugs in New Bordeaux in exchange for his financial support. Santangelo's only request is that he be allowed to kill Lincoln Clay.
When Santangelo attempts to ambush Lincoln in the French Ward, his men are killed and he's fatally wounded. As he lies on the ground dying, he utters one last racial insult at Lincoln, who states "My name is Lincoln Clay" before plunging his knife into Santangelo's throat, killing him.
- Santangelo may appear at the end of either Burn Like Napalm, Certainly Was Exciting or Real Nice Time.
- In Comes the Devil (killed)
- Santangelo is one of the few targets to not have a bio in the Kill List, along with Judge Holden, Remy Duvall, Ritchie Doucet, and Giorgi Marcano.
- The dialogue between Sal and Santangelo will be different depending on which capo is killed second.