The next step for D&D has to be the no-fantasy settings, but the d20 system is not ready to be retrocompatible. Sentient enemies with firearms are too dangerous, and then these need a different value of challenguing rating or XP reward. Have you played any Battle Royal where you start without weapons?
I say "Cobretti effect" because in the movie "Cobra" the female main character, Bridgitte Nielsen, couldn't face the "night slasher" but the main character, Sylvester Stalone, with enough weapons and ammo, he was an one-man-army who could defeat the cult of the new dawn. In the first movie "Alien, the eight passenger" one xenomorph was enough to kill almost all Nostromo's staff, but in the sequel thanks the sentinel turrets dozens of them, maybe hundres, were killed from a separate room. In the first confrontation between Robocop and the robotED-209 our friend the agent Murphy had to run away, but later in the final part of the part with the Cobra assault canon only one shot was enough to destroy it. Other example is in Survival Horror videogames when the player starts with nothing, but later with the right weapons and enough ammo special mosters can be destroyed more easily, some times even too fast.
A psyco-killer with a knive can be a nightmare for PCs in a survival horror game, but the same enemy is only walking XPs if the PCs are soldiers or a S.W.A.T. team.
Some enemies are designed for meleet fights and others for PCs with firearms. The champions of Street Fighters can't face againts the characters of Overwatchs, or the martial artists from Mortal Kombat aren't ready to face the infernal creatures from "Doom".