From the perspective of a server-sided anticheat as client side exists as a barrier to entry so it must be intrusive to work. I know of non-cheat devs who have bypassed Vanguard accidentally while implementing low level windows stuff.
No, this isn't possible. There will always be purely client sided cheats that don't touch anything sent to the server. For example, seeing enemies through walls gives a huge advantage but isn't detectable. This can be mitigated only sending entities the client can see, but latency makes it so you can't fully stop this.
You can also attack latency which doesn't directly affect protocol. Rewind enemies slightly forwards or backwards in shooters so you land the shot when you aim slightly off. These cheats exist in CSGO.
However, an anticheat's job is to prevent other players from noticing you cheating rather than to prevent cheating. This key distinction does let you simply ignore a lot of purely client side cheats as insignificant.
You also can't do much about aimassists that slightly correct aiming. Machine learning can help here but falls apart quite fast when humans are covering up the machine's aiming patterns. Algorithmic inputs and random human inputs still result in random-ish human inputs.