Machete is tasked by President Rathcock to take out Voz after trying to start a nuclear holocaust on Earth. Before his mass exodus to a space station which he built. While kidnapping revolutionary Luz who is frozen in carbonite. Along with a bunch of Mexican-Americans who are forced to work/build on the space station.
- Danny Trejo as Machete Cortez
- Michelle Rodriguez as Luz
- Mel Gibson as Luthor Voz
- Daryl Sabara as Julio (rumored)
- Sofia Vergara as Madame Desdemona
- Marko Zaror as Zaror
- Carlos Estevez as President Rathcock
- Lady Gaga as La Cameleon
- Penelope Cruz may play the third and new love interest of Machete, after Sartana and Miss San Antonio.
- Miss San Antonio may be revived by Voz's healing pool.
- El Cameleon may have survived, and his La Cameleon disguise with a male voice, may hint his true face.
- Voz's face may be changed into the face of Leonardo DiCaprio by one of his doctors.
- Rathcock may be a traitor to make marijuana legal.