Here are some useful examples of valid and invalid locations of ultra secret rooms. If the level generation works as intended, you will only need to create one red room to find the ultra secret room, as it is revealed immediately after you open the neighboring red room. The level usually has 3+ possible spots for an ultra secret room, but if there aren’t any valid spots for these rules to apply, the second rule will be disregarded. Under normal circumstances, an ultra secret room will be generated between 2 (sometimes more) red rooms.
Since red rooms cannot be created in greed mode, ultra secret rooms are limited to regular runs. The Crystal Key trinket opens red rooms too, but you can’t control it so it won’t be very helpful here. Obviously, the most reliable one the Red Key, but you can also use Cracked Key or Soul of Cain. In order to find an ultra secret room, you will need an item/consumable capable of creating red rooms. This can be circumvented if you have a trinket that allows those rooms to spawn on late-game floors, like the Wicked Crown or Silver Dollar.
