In what you are describing, they are still the same setting, just with the focus pulled further out.
Well, no. Not "pulled out" - that would imply the overall focus is more broad, which it does not have to be.
For example, at the end of their last campaign, they did some funky stuff with the gods. They could, for example, use a different ruleset (say, Daggerheart) to look at the impact of that on a world other than Exandria*. While someone might quibble that is still "the same setting", when it is literally a different planet/world, and none of the old setting materials or lore apply, that's a pretty weak quibble.
In the Forgotten Realms, rules edition changes tended to coincide with major cataclysmic events in the history of the campaign world. Maybe for Critical Role, change of rules might come to coincide with change of world.
But if the next game is Cyberpunk Red for the system and setting, it's a new animal.
Maybe, maybe not. If, in Cyberpunk Red, on a different world, they are continuing that story line of what the gods are doing now? They are not bound by our preconceptions, after all.
While I don't expect them to go that far afield, there's no real call to pre-choose how to categorize what they might come up with. They are clearly creative folk. How about we let it happen and see, hey what?
* I considered calling this hypothetical world "Inandria", but decided that'd be dumb.