There was a lot of hostility between Vincent Price and Robert Quarry, particularly when Price discovered that American International Pictures was planning to replace him with Quarry as their major horror film star. At one point, when Price discovered Quarry singing opera, Quarry said "I'll bet you didn't know I could sing, did you?", to which Price replied "Well, I knew you weren't a fucking actor."
This film was intended to be the second film of a planned trilogy. The third film would have featured Dr. Phibes either fighting a group of Nazis or searching for the key to Mount Olympus. Among the titles mentioned for the third film were "Phibes Resurrectus," "The Seven Fates of Dr. Phibes," and "The Bride of Dr. Phibes." Proposed stories for it included Phibes being the subject of an elaborate revenge plot by Lem, Dr. Vesalius' son from the previous film, and Victoria Regina Phibes finally being resurrected from the dead, but becoming a deranged homicidal maniac far worse that her husband ever was. Reportedly, a large number of sequel scripts were written, all exploring different story ideas. There was also a plan to bring Dr. Phibes to the small screen in a TV series, in which a reformed Phibes fought crime. In the 1980s, an updated Dr. Phibes film was proposed as well. Unfortunately, Price's departure from American International Pictures and AIP's subsequent change of focus to films which would be of the exploitation/grindhouse genre meant that the third film was never made (nor any further films beyond it).
Vulnavia was originally going to be a new character, but the studio insisted on keeping her name. That explains why the character returns, despite being killed in the previous film, L'Abominable Docteur Phibes (1971).
Peter Cushing was originally cast in Joseph Cotten's role in the previous film, L'Abominable Docteur Phibes (1971), but withdrew due to his ailing wife's health. He was able to supply a cameo in this film, a day's work (the film was shot in December 1971).