Okay I am sorry, I am sure this have been covered to death but I looked and I couldn't find anything conclusive. Is the Great Wheel canonically how the Realms cosmology works now? If so, where are the extra planes like Dweomerheart and the House of Knowledge? Outlands, or incorporated into the Outers?
Yes, the Great Wheel is back with some alterations borrowed from 4e (like the Feywild and the Shadowfell). The divine domains are now likely incorporated into the Outer planes. Dweomerheart/Mystra's realm used to be in Mechanus, IIRC. 5e doesn't say anything specific about the divine domains, so you might as well use the 2e info for them (their position in relation to the Outer planes is explained in "On Hallowed Ground").