For example, let's say you need to do Shift-Option-F12. First, you need to hold a modifier to bring your F key layer, possibly a separate or chorded modifier to get you to the F-keys above 10 since you only have have 10 numeric digits. Then, that needs to be compatible with both your shift modifier AND your option modifier, which with only 2 thumb keys per side it probably won't be. So, then you think, oh no worries, I'll just set up a single shortcut that does what I need, but then you end up with a profusion of shortcuts that you need to remember.

I've found that in practice, I can't really go much below 58 keys and 3 layers without requiring tap-and-hold or losing some of my less-frequently used chars (` comes to mind), so I can sympathize with the ancestor posts.