Not really, Dx/OpenGL injection still functions I believe, so long as the app is a standard windows app. And if the dev wants to support mods, it certainly be possible. But yes, likely anything that intends to mess with the executable won't work unless it's exposed deliberately by the developer.
In my ideal world Dev would implement denuvo for the first 6 months or so, with proper mod support - all data files and references available outside of the executable, preferably with a toolset that allows access to some of the running game's memory via API through Denuvo.
Then in 6 months or so, denuvo is removed in a patch for full third party mod access.
Well, actually in an idela world people wouldn't pirate PC games