The point of no return will warn you when you get there, as it did in act 1 and act 2. There is the usual pretense of urgency but I've been incapable of triggering a forced ending no matter the amount of long rests. There are brief, small changes to at least two locations in the city after you take down both Orin and Gortash but those will end when you've been there. Shouldn't lock you out of any quests. You can do the House of Hope at any point as well. Getting the Orphic Hammer does not lock you out of content and it's actually one of the most rewarding areas. Not getting the Orphic Hammer can be bad.
