I generally run every campaign in it's own homebrew setting that has characteristics that make possible the central themes of the campaign. I have run one setting for two campaigns in a row, with basically the same group of players, 80 years later so they could see the effects their heroes had on the world but exploring different aspects and for the most part different geographic places.
Currently I'm running a setting where the world itself is the body of a dead god, with the moon the decapitated head. That deity had been drawn into a plane with next to no other power sources in order to be killed, so that body (and orbiting skull) are the only sources of magic. The party formed as each of the characters had awoken an Imperial Mask, each a sentient and powerful artifact (supposedly) from the peak of the Imperium. Most of the masks slumber, only awakening when someone compatible is chosen. This made the characters important and influential at the beginning of the campaign leading to being able to do very different low level play then clear out those rats and various fetch quests. The Imperium is failing, has been failing for a long time, and there are many signs of high magic and magic-as-technology all about but they barely work - a sky tram across the capital city has a single working car left, and it requires a wizard in there constantly feeding it power.
Dwarves have been genocided, and the drow are a created race to inhabit their place underground and continue to mine the Bones of the Earth (literal) for the Imperium. The halflings are also a created race, servitors and agricultural workers. (The genocide and the created races were from player suggestion/request during Session 0.) It has later come up that the nobility of the Imperium are also modified humans, to be better, though the bloodlines have mixed some with normal humans. This was a plot point but also conveniently described racial Humans vs. variant Humans in the PHB.
The seas, after a point, are far enough from the land (the body) that there is no magic, so all of the discovery of continents and such had been ones close enough. But now with magic failing and navigation on the seas becoming perilous they have discovered other, non-magical ways and a new continent has been discovered. The Imperium has started a colony over there, and the land is plentiful.
The Child-Empress Olixia, sixth of her name, saw six masks awaking at the same time, something unheard of in many generations, and determined they should stay together - to be sent to the new lands she believes is the future of the Imperium. So the group started with being sent there.
To discover that it was also full of magic. Dragons are (supposedly) extinct on the continents the Imperium can reach, though a skeleton of one is in the Imperial Library. Here they saw (and avoided one). Met as ambassadors to a powerful and established empire (needed to flip colonialism on it's head). They realised that fabled lost spells - those of the 7th and higher level - would actually work over there, that their land had been mostly drained of magic through long, flagrant and extensive use of it.
But I've got half a dozen new setting ideas fleshed out to a degree in a document, and more than that in a nutshell format. I have more setting concepts then I will ever get to run campaigns. (My last campaigns all completed, but were 4 years, 7 years, and 4.5 years long.)