The MCU's comicbook source material is not known for rebooting itself on a grand scale and wiping-out its previous continuity. I doubt Marvel Studios would do differently. If its ever going to do a "reboot", i would imagine it would be similar to Star Trek's Kelvin timeline. You create a brand new continuity where you could play around with old characters (2009 Star Trek movies and its sequels) but has a clear connecting line (and properly onboarded fans, thanks to Nimoy's Spock Prime) to the old but still active continuity(Picard, Star Trek Discovery).
I think lack of F4 and Mutants will be the thing here, alone with maybe Fiege moving on. I could see the universe having to be reboot, multiverse's once again cut off and a new timeline can begin with Mutants, F4 and Spider-Man all planned from the jump. However I can't see that until after Secret wars but it would be a great way to end the current iteration of MCU and let something different start again one day. Having those other properties from the start will let them make a very different MCU for us.
However this also means in ways that the MCU never ends it just gets a narrative reasoning for the reboot