The following is not meant to be snarky in any way, but on the whole, no, it doesn't make sense.
Configuration profiles can be set up to either be manually triggered (which is usually the exception) or automatically triggered (more common) when you land in an application. The things specific to that profile will only apply when that profile is active.
Now, on to what I think you're asking (and I could be wrong): If you're looking for the same Synth to pronounce the exact same thing differently depending on what application you're in, would only be possible using "clever trickery." The dictionaries, temporary, default, and voice are separate. Both the temporary, which vanishes if you restart NVDA and default apply no matter what voice and what app you're in. Now, the voice dictionary applies in any app you're in where you happen to use the specific voice, so if you were willing to change voices based upon the application you're currently using, you could limit substitutions to occurring only when that specific voice is in use. I'm not sure if a change in voice, as opposed to a change in synth, can be made automatic in a profile, but the change in synth can, and you could just make sure you're using a specific voice with that synth for which you created the necessary voice dictionary entries.
I hope this helped, and I hope I've managed to actually get at what you were hoping to do.
Brian - Windows 10, 64-Bit, Version 21H1, Build 19043
The difference between a top-flight creative man and the hack is his ability to express powerful meanings indirectly.
~ Vance Packard