So far the cause is not known.
Well, in most cases it's just RenPy - it's not really the most performant engine imaginable. If you then add some devs using unoptimized assets on top of it, I would say you already cover at least 80% of cases suffering from poor performance. Sure - the systems the games are run on are relevant to a degree as well - but RenPy isn't that great of a engine when it comes to performance - similar to Unity. And the reasons are usually known - but fixing them is not exactly the main focus of development.
In the particular case of L&S:SB the problems are also tied to the development practices as well - there are multiple aspects of the game that could be vastly improved on a conceptual level, that would reduce performance-impact further. It's nothing that solely have to be done on a technical level of the framework - it's often also tied to HOW devs code/develop on such engines.
L&S:SB suffers from a pretty poorly approach to navigating 'the world' that could be highly improved and/or streamlined to reduce asset-loading - at the same time such changes would improve the overall feel of the game and reduce the 'felt' grindiness many people regularily mention.
Unfortunately that's pretty much standard - what you can expect from non-professional coder/developer - and you can't really blame them, because you have to know one or two things about it to improve your own game/programs accordingly. Especially in this 'genre' of games it's usual that you deal with artists who learned enough to make things work - L&S:SB is even a rather elaborate project compared to the state of the scene. Still - even with RenPy getting more and more optimized - without elaborate structural changes games like this one will suffer from performance-issues. Devs could counter that problem with proper design-choices - but unfortunately that's usually not something they are mainly concerned with...
