Depending on what the layout of North Underrail actually looks like, Hexagon might be too important or central to the region to expend on a standalone story, so to speak. Everything about the city would have to be designed and implemented for Infusion, and without some exceptional shenanigans, most of those design decisions would then have to carry over to Underrail 2. Essentially, the developers would be limiting the possibilities of a part of the actual sequel before they even started working on it. It could also be a bit jarring to first introduce a Hexagon that's massive enough to be the setting of Infusion all on its own, and then reduce it to a smaller version that didn't completely overshadow all other locations of Underrail 2 in size. Not impossible to achieve, but it'd be another headache the devs could easily avoid by picking a different setting.
Naturally, that all assumes that Underrail 2 is going to be a thing, and that's it's going to take place in North Underrail.
As for my own guess, I don't think Infusion's going to be set in North Underrail, but it will probably still take place somewhere that's relatively close to South Underrail. If the 3D meshes we've seen so far are anything to go by, people's outfits as well as crawlers look very similar to their counterparts in the first game, and they probably wouldn't if the new setting was going to be a location far away on the other side of the world.
