Manolo Santander is a Criminal.
Manolo is encountered during the mission "Lucky in Love", during which he is playing a game of poker with Andreas Müller, Landon Ricketts, and the Stranger. However, Ricketts invites John Marston to join the game, and shortly thereafter, Müller accuses Marston of cheating. Guns are drawn, with Manolo pointing his at Ricketts; the group finds itself at an impasse.
After Marston kills Müller in a duel, the Stranger takes a nearby woman hostage, and threatens to kill her with a knife. Despite him using the woman as a shield, Marston is able to shoot him in the head. Manolo then attacks Marston and Ricketts along with Selestino Herrada, an unknown Criminal woman and Rigoberto Artiz.
Despite being killed, he can be encoutered at the Tesoro Azul Gang Hideout, where he will be hostile, and some Random Encounters involving Criminals, such as a store robbery or a prison wagon escape. He can also be found playing Arm Wrestling at El Matadero.
- Even after his death, he can be seen gambling throughout Mexico.
- At the Tesoro Azul hideout, he serves as a mini-boss, who emerges from a building along with two other Criminals, after a certain number of enemies have been killed.