During the seven-year gap between the first Sin City (2005) and the beginning of principal photography on this film, Brittany Murphy and Michael Clarke Duncan both died, forcing Robert Rodriguez to re-cast their respective roles of Shellie and Manute (Dennis Haysbert). Due to Devon Aoki's pregnancy at the start of production, the character of Miho was also re-cast, with Jamie Chung replacing Aoki. Jeremy Piven also ended up replacing Michael Madsen as Bob.
The lead role was originally offered to Johnny Depp, but he declined due to scheduling conflicts. Joseph Gordon-Levitt later replaced him, despite offers to star in other movies such as Guardians of the Galaxy (2014) and Godzilla (2014). In 2006 when Rodriguez first started putting together ideas for "Sin City 2," he considered Depp for the part of Wallace, the lead character of "Hell and Back," which he was hoping to adapt as one of the film's three segments. The idea to adapt "Hell and Back" was scrapped, however, and Rodriguez chose to adapt "Just Another Saturday Night," "A Dame to Kill For," and the never-published "The Long, Bad Night" instead.
Although she played a supporting role in the "A Dame to Kill For" comic book, Frank Miller and Robert Rodriguez retired the character of Shellie from the film version instead of re-casting her, out of respect to the late Brittany Murphy of Sin City (2005).
Two of the film's four segments, "Just Another Saturday Night" and "A Dame to Kill For," take place before the first Sin City (2005) film.
The MPAA banned one of the movie's character posters. The poster showed Eva Green as Ava Lord wearing a sheer gown through which her nipple was visible. Green told "Vanity Fair" about the controversy: "I'm not actually naked on the poster. I find it a bit odd. It seems like it's all just publicity, a lot of noise for nothing. You have so many more violent things in the movie business, and this is kind of soft. I'm not naked. It's suggested. I find it really sexy, actually. It's kind of beautiful. But if it shocks people, I don't know what to do about it. I don't want to upset anybody. I don't want to be seen as just the femme fatale or put into some silly box. I hope that people will have enough imagination."
Robert Rodriguez: When Nancy has the television on in her apartment, the two bums in the show she is watching are played by Frank Miller (writer and honorary director) and Rodriguez (director).