There's a whole lot of folks that believe minimizing have movement is ergonomically better, if not faster, and therefore use keyboard layouts that require cords to type not just function keys but also numbers.
A popular way to handle modifiers, for example, is putting them on the home row. A tap gives you a letter; a long press gives you a modifier instead. This allows me to (for example) type Ctrl+alt+shift+left arrow without moving my hands at all.
Home row mods are really finicky though. It took me months to get really consistent at them.
What arlort says: ASDF and jkl; both have the home row modifier behavior, so you can hit any combination as long as you have both hands on the keyboard. So Ctrl+shift+a is pressing and holding k+l and tapping a. Holding d+f and tapping a would also work, but it would be uncomfortable. Miryoku[1] is a popular layout in this style and was my starting point, but I think it's often customized.
The "both hands on the keyboard" thing is a major caveat. The key I use to switch to my navigation layer (arrows, paging) is on my left hand and it also runs all of my non-home row keys into Ctrl modified versions of themselves. This allows me to type almost any Ctrl combination while mousing that you could type easily with only your left hand, with the exception of Ctrl+D because I have D mapped to control (I use super/alt/Ctrl/shift). I only use Ctrl+D in the terminal, so I had no need to resolve this limitation.
Is all this worth it? Honestly it's hard for me to say yes, but I also find using a qwerty keyboard uncomfortable now. Plus the keyboards are cool.
You can change the behavior of your layer activation key(s) so that you aren't n+1ing your buckies, and can also customize the keymap of all layers (including the baselayer) so that you don't have Ctrl and A sharing the same physical key between layers to avoid that exact issue. Though, if you do choose to do that, there is still a way to send Ctrl-A (using one shot keys [2] for example). I've listed a few options you have for your layer activiation key behavior from the qmk wiki [0] as it's more succinct than the zmk wiki [1], but QMK and ZMK (which the Ergo S-1 uses) both share similar functionality in this way. Non exhaustive list of layer-activation behavior from the QMK wiki:
> MO(layer) - momentarily activates layer. As soon as you let go of the key, the layer is deactivated.
> TG(layer) - toggles layer, activating it if it's inactive and vice versa
> TT(layer) - Layer Tap-Toggle. If you hold the key down, layer is activated, and then is de-activated when you let go (like MO). If you repeatedly tap it, the layer will be toggled on or off
You can also use Macros if you'd prefer (but not required) to handle triple (or more) buckies, which both ZMK and QMK firmwares support.
I will note that this Ergo S-1 seems to be missing at least 8 keys that most other Ergodox keyboards have (the 3 keys of the inner column on each side and the bottom right and left corner keys) so total physical keycount appears to be closer to a 60% kb. So in that way, you're going to be more dependent on using layers (or Macros) in general than even other ergodox (such as the Ergodox-ez [3] style keyboards of this type.
EDIT: Apologies, I wasn't paying attention to usernames when responding to comments and basically gave you this answer twice across two different comments. Deleted the other as this one is more complete/to the point.
Only been lurking in the split ergo keyboards so far, but I believe what people do is they have the home row modifiers on both sides, so if A is Ctrl to have Ctrl-A you'd do ;-A
A popular way to handle modifiers, for example, is putting them on the home row. A tap gives you a letter; a long press gives you a modifier instead. This allows me to (for example) type Ctrl+alt+shift+left arrow without moving my hands at all.
Home row mods are really finicky though. It took me months to get really consistent at them.