(And I don't even want to think about having no F-keys - which would require even weirder key-combinations in many cases.)
In general though, custom mechanical keyboards have firmware that can be programmed with "layers": hold down a certain key (or toggle) and layers get activated which changes the meanings of keys. This is the way those very minimal keyboards (which doesn't even necessarily have a number row) can work for daily use. If you want the keys badly, just program your firmware appropriately.
I do not have F-keys in my default layout, and I don't miss them as I rarely used them on a normal-size keyboard anyway. But if I do need them, they're just one layer shift away: Fn+1 gives me F1.
Do note that layers can be activated permanently, not just through chording. In my layout, tapping Fn twice turns the right half of the keyboard into a numpad layout so I can do quick data-entry. And in that layer I also have a Tab key under my right hand so I can do both horizontal and vertical data entry. On a normal keyboard, the missing Tab key always forced me to keep both hands on the keyboard when using the Numpad.
MacOS has two sets actually, one with command and arrows and one with control using Emacs shortcuts.