There's definitely a lot of nods to Old Sharlayan lately but I think a more likely "Crystarium" for 6.0 is Radz-at-Han. It has been firmly established as a peculiar place right next to Garlemald, yet completely independent. If we are to set foot on Ilsabard, I would think it would be through Thavnair.
I think the expansion will be split in some way between Thavnair, Garlean Empire and Meracydia. Thavnair will be our vector of attack/home base and we'll see 1-2 areas in southern Garlean Empire that will be used to humanize the average Garlean. Following this I believe Garlemald will be invaded by a third party that had thus far been kept in check while the empire had real leadership.
I believe this will be the Meracydians, mainly due to YoshiP's advice to brush up on HW's story. HW's most interesting revelation for the future of the plot would have to be that Meracydia is both the source of the "original" (not quite so anymore) primals/eikons and the home of Bahamut, both of which even the Allagans struggled to defeat. I think we will travel directly to Meracydia to confront this new threat and in the course of that learn all manner of new things about the world that will become relevant for the next story arc, as well as information on how to deal with Zodiark. The fact that Meracydia is the birthplace of modern primals, the Garlean Empire has a core mission of destroying primals and we now know it was established by Emet-Selch, who is himself beholden to a primal, may suggest that Meracydians have access to magicks that would threaten Zodiark's existence.
This is a little more out there, but I think there's a strong possibility of most of the empire being destroyed by a calamity.
As far as I know, Zodiark is currently lying dormant inside/as the moon and needs one more rejoining to tip the balance and reawaken. I doubt they would wrap up this story without letting us fight Zodiark himself. Since nothing in the game world can ever change in a meaningful way, large-scale destruction can only happen on Ilsabard, as it's unexplored territory. Doing this would also allow them to wrap up Ilsabard in one expansion, even though it's roughly the size of Aldenard and Othard combined. Since Zodiark is trapped inside the moon and presumably awakens soon, it could potentially mean that the moon itself crashes into Ilsabard much like the fall of Dalamud. Thematically, this would mirror the start of the arc, foster reconciliation between the powers through a shared experience and potentially let us take on the role of Louisoix by preventing complete annihilation.
Or, a more simple option, it could just be destroyed by the attacking Meracydians.
The final/??? map in the game could be in the north around a destroyed Garlemald, with the significantly ravaged city itself acting as our endgame hub and slowly restored through "Garlemald Restoration".