A fraction of it has to do with renpy itself not being designed in a way suited for this manner of sandbox, but that's just a fraction of it, not to mention other sandbox games have been made on renpy with acceptable performance. It also has to do with Oni being first and foremost, an artist, and not much of a coder, so you've got tons of redundant and repeating codes attached to each task running in the background, bringing the performance to a crawl.
Yea I've noticed that latter one, when looking at mods for the game, the number one complaint for why it takes so long is because under the hood it's massively spaghetti code.
The problem with games like this, is that it can be really really simple code if you know what you're doing, but hell if you don't. Most the background are basic conditional statements, most the behaviour of the girls are exact copies (instances), and most the rooms are relatively the same.
What I imagine is that Oni either didn't use classes and thus has a ton of repeating code everywhere, or hasn't made a proper class structure.
I wouldn't even put too much blame on RenPy, I've seen other games do more with less issues, granted Python is slow af and trying to do applications that are more governed by instruction complexity rather algorithm complexity is silly to do in Python, this game should be able to handle it