GTK+ 3 was a bit of a nightmare in this regard, but GTK+ 3 is also feature frozen and will be supported for more years to come, so a new application doesn't have as much to worry about here.
The downside would be the desire to port to GTK+ 4 in some amount of time, which might require a large amount of effort depending on the application. On the other hand, if you're starting today you could also start with GTK+ 4...