The plot of DmC: Devil May Cry was written by director Tameem Antoniades, while film director and writer Alex Garland is credited as a story supervisor. Although he worked extensively with Antoniades on the writing and design of Ninja Theory's previous game Enslaved: Odyssey to the West, he had very little known involvement with the development of DmC: Devil May Cry. Antoniades claimed that Garland warned him to be prepared for death threats over the game's drastic changes from the rest of the series, and that "although I'm writing I'm still under his consultation." Conversely, when asked about his involvement in a 2025 GQ interview, Garland only replied with: "Yeah, no, I did fuck all on that."

In the intro cutscene of the Definitive Edition on PlayStation 4 and Xbox One, Ninja Theory removed a line of sexual dialogue between Lillith and Mundus. According to the developers it was removed to improve pacing, and because "We didn't like the line."

The cutscene that plays after defeating Spoiler:the "Succubus" in Mission 6 was removed from the Japanese release, likely due to Spoiler:the sexual nature of the scene.
However, this scene was not removed from the Japanese "Definitive Edition".

Dante's character redesign shares resemblances with the director of the game, Tameem Antoniades. Tameem stated in an interview that he did not intend for Dante to look like him, as he explained that Dante is "a decade and a half younger than me, way better looking... The only thing he's got is black hair. And he's male. I didn't design the character. I didn't go to our designers and say, 'I think it's a really good idea if we make the new Dante look like me, because I want to be in the game.' They'd laugh at me. They'd throw me out the window."

During the opening cutscene, a number of posters for the band "Combichrist" can be seen on the side of each TV. Combichrist provided the soundtrack to the game.

During a cutscene in Mission 1, a long, white wig falls on Dante's head. After looking at himself in a mirror for a few seconds, he says "Not in a million years." This is a reference to the past Devil May Cry games where Dante had long white hair, and fan reaction to his new character design.

The first time Dante uses the Ophion Demon Pull ability to grab an enemy, he'll shout "Get over here!", a reference to the catchphrase of Mortal Kombat's Scorpion, who says it when using his spear attack, which pulls enemies close to him.

Throughout the game are a number of arcade cabinets. Some of them display both Ryu & Ken from Street Fighter II. There are also a number of "Giant Enemy Crab" games, a reference to the E3 announcement of Genji: Days of the Blade.

All of the trophies and achievements in the game are named after one-liners and quotes from the previous games in the series. This sort of tribute is also present in the add-on "Vergil's Downfall".