William Lustig was originally going to direct True Romance (1993) before Tony Scott. During that period, Quentin Tarantino and Lustig discussed Tarantino writing Relentless 2 and Tarantino was excited. The two thought they would be like Scorsese and Schrader writing Taxi Driver (1976) together. However, the relationship soured when Lustig demanded rewrites on True Romance.
Joe Spinell was originally cast to play the role of Captain Blakely, but died shortly before filming was to begin.
Relentless was also the original name for Sam Raimi's 1985 comedy Crimewave. Raimi allowed director William Lustig to reuse the Relentless name and it was because of that, it lead to Raimi getting a shout-out in the end credits.
Relentless marked the first time that Joe Spinell turned down the chance to work with Bill Lustig. Lustig wanted to fly Spinell out to Los Angeles for a scene in the film but Spinell declined, saying "I can't do it, Bill. I lost my false teeth. I don't look good."