The school setting is getting old. I don't know how long we can keep using it before things become repetitive. I really don't even know what's gonna happen to the series in 10 years. Maybe it'll hit the same situation the Legend of Zelda has.
I don't think using the same setting matters that much. SMT games (numbered entries) have been using Tokyo as a setting since the very first entry, that franchise is over 20 years old and they still manage to do new things and make each entry feel different from one another while following the framework they've stabilished all those years ago.
The thing that could make Persona feel same-ish a few entries from now is the calendar system, which pretty much dictates the pacing of the game and somewhat limits what they can do with it storywise since they need to follow a very specific set of "rules" (the story
needs to fill the entire calendar year, there
needs to be periods of downtime for the player to catch up with their social links and so on). I feel like it's too early to be having this discussion anyway, most of us haven't even played P5 yet to begin with.
Besides, if they really want to do something different without alienating the current Persona fanbase, there's nothing stopping P-Team from making another spin-off series under the MegaTen umbrella. I'd actually be more excited for that since it would mean they could go nuts and do something completely new without fear of it angering Persona fans. Not to mention that'd space out entries in the Persona franchise (which would help in avoiding franchise fatigue) and give Atlus plenty of time to milk each release as much as they want while still giving us something else of similar quality. Hashino directed vanilla Nocturne, DDS and Catherine so I fully trust his capacity to deliver something new.