D&D 2024 Greyhawk is a "heroic fantasy" setting, but can accommodate other genres as well. Forgotten Realms is "epic fantasy" but likewise can accommodate.
The most requested "new" settings are, in order:
Sword and sorcery (personal ambitions and violent challenges, morally ambiguous, with only low magic that is often villainous).
Heroic Fantasy (where individuals tend toward Good, and involve cosmic conflicts and high magic, but rarely at high levels).
Wuxia (often emphasizing flashy, personal, warrior magic).
Dark Fantasy (generally involving Evil and hopelessness, with Undead, Fiend, or Aberrant, but protagonists might be heroes or antiheroes) (somewhat like sword-and-sorcery but with high magic).
Urban Fantasy (modern magical realism, often Humans with high magic, in romances with other species, such as Elf or Vampire).
Is it possible to combine these into a single genre fusion?
A main decision is between medieval "swords" versus modern urban "guns". But perhaps medieval can have guns (like Critical Role), or modern can have swords (like Highlander). Or the choice of weapon is unimportant (like superheroes).
Maybe most of the setting is like modern mundane reallife, while the magic happens in the Ethereal Plane that overlaps the ordinary Material Plane. Perhaps the ether itself is a digital "augmented reality" overlaying reallife persons and places.
The setting might be Human only, except nonhuman species inhabit the ether.
Magic in the mundane world is rare. But the ether can feature individuals with high magic to influence the ether. Certain material locations are set up to interact with the ether (like to 3d-print a nonhuman creature or a remote avatar of a Human). These interactive places tend to be rare, expensive, and secretive.
Mostly, the conflicts derive from personal ambitions and situational ethics. But a looming threat might involve sinister Fiend or Aberrant or Undead conspiracies.