Loosely, in the way GTA games always are - same continuity, same satirical version of America, new cast and new state. If you have never touched GTA V, nothing in GTA 6 is going to be lost on you.
Shared world, separate story
The series has run on the same rebooted continuity since GTA IV, which is why brands, radio stations and running jokes reappear from game to game while the characters do not. Los Santos and Leonida exist in the same fictional country. That is a matter of set dressing rather than plot.
Returning characters
None have been announced. Rockstar has introduced Lucia and Jason as the leads and has not confirmed any GTA V character appearing in any capacity. Every cameo prediction you have read - and there are many, usually involving the same three names - is speculation. It is also worth noting that GTA V’s cast is roughly a decade older in-fiction by now, which limits what a cameo could even be.
What genuinely carries over
- The universe and its brand names.
- Radio stations as a format, though no station list has been published.
- Structural DNA: an open state, a criminal escalation, mission variety built around driving and shooting.
Do you need to play GTA 5 first?
No. Playing it first will make you notice a handful of references you would otherwise skim past, and it will give you a baseline for judging how much the series has moved on in thirteen years. Neither is a requirement, and neither is a spoiler risk in either direction.
The GTA Online question
GTA Online belongs to GTA V and has no announced relationship to GTA 6. No separate online mode for the new game has been announced - not its contents, not its timing. Our page on GTA 6 RP and online covers what is and is not known there, and the setting itself is broken down on the map page.