So the game would be centered around a location - a building - that can move as time passes and Wastes build. It reaches a certain point and the building literally moves, often from one city to another, and takes on a new appearance and shape. The alchemy involved makes the average populace just assume it's always been there and ignore it. Within the building, Azoth is masked to outsiders (Pandorans, Centimani, alchemists, etc.), Pyros use is masked and no Wasteland forms. OUTSIDE, however, all is as you'd expect and all bets are off. A cell phone is always kept within the building that all residents can call if they are out when a move happens (there's never any warning) so they can find out where to go. They still have to travel to get 'home', or have someone come get them, but few get truly left behind.
Also, this would a be a Promethean-only game in the strictest sense - Chronicles of Darkness, God Machine, and all other spheres and lore aren't a part of it. The Refinement of Silver is not used/canon. If anything else supernatural is out there, it'll come up IC. Human Alchemists exist and are a known danger, however.