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.
