- B-Team Sequel: Because David Cronenberg and his Production Posse had moved on to Dead Ringers, this film featured an almost entirely new creative team. The key exception was Chris Walas, who had designed the makeups and special effects for the first film and was promoted to director here.
- Executive Meddling: As related by Frank Darabont in Fangoria Magazine, meddling was rampant. The screenwriters wanted to explore a number of themes, among them an exploration of what it means to be a son to a father. Those themes were dropped in favor of Squick and Gorn. Darabont says that at the first screening, Chris Walas turned to him at the film's conclusion and said, "It's not the movie I wanted to make, either." Mel Brooks reportedly remarked that, "In all my years, I have never seen such vile studio interference on a project." The worst thing? All these decisions were made by executives who hadn't even seen the first film.
- Name's the Same: Seth's son is called Martin. Martin Brundle is also the name of a British former race car driver; the surname's use in the original film was a deliberate Shout-Out to him as David Cronenberg is a huge racing buff (and an Ironic Name in-joke as Seth hated vehicles due to chronic motion sickness), so the sequel sort of brings things full circle.
- What Could Have Been:
- Geena Davis was reportedly involved with an alternate sequel in the 1990s, to be directed by her then-husband Renny Harlin, titled Flies. The script was said to feature a story where Veronica does not die in childbirth and instead gives birth to twin boys, and may have been one of the earlier original concepts for this film.
- The first storyline speculatively planned for this film involved Veronica discovering that Seth's human mind was still active within the telepod systems, requiring her to work against Bartok Industries to try and use the telepods to restore Seth's human body.
- In The New '10s David Cronenberg himself wished to do a follow up film that was (in his words) "more of a sequel or a sidebar." Budget constraints among other things kept the film from moving forward.
- The 2005 Special Edition DVD release was supposed to include a commentary from critic/filmmaker Drew McWeeny and DVD producer/filmmaker Charles de Lauzirika (the latter most famous for his work on the Alien Quadrilogy and Blade Runner: The Final Cut sets) but though it was recorded, it was dropped. In a bonus episode of the former's podcast '80s All Over, Drew just says that "I think we told too many stories" — suggesting that they went into too much detail about the Executive Meddling it faced.
Trivia / The Fly II