Almost all API requests are paged, so the library size shouldn't matter
too much if you're just interacting with the API, but you'd want to do a
lot of local caching [1] to avoid having to repeatedly make a huge
number of small requests.
Not clear to me whether you're saying you would use the desktop app or
the web library as well. We know that some people do manage to use the
desktop app with hundreds of thousands of items, though we don't
currently do much testing with libraries of that size.
If something isn't performing well, you can let us know and we can try
to improve it.
- Dan
[1]
https://www.zotero.org/support/dev/web_api/v3/basics#caching