The plasma rifle is very effective against strong enemies such as the Albino Cyclops and T-Mech. Its rate of fire and amount of damage allows it to quickly shred them to pieces.
The plasma rifle is not effective against small and/or fast moving targets such as Yagoda the Witch and the Floater because its projectiles take some time to reach a target. While it usually takes a few shots to kill those enemies with the plasma rifle, the player wastes too much ammo trying to kill one because of their erratic movement. Switching to a bullet-firing weapon usually produces much better results because bullets will hit something as soon as they are shot from a gun.
It is also not very effective against enemies that tend to move around while the player is at long range, such as the Kozak Helicopter. The projectiles fired by the plasma rifle will be too slow to hit the target before the target manages to move away from where the crosshair is pointed at.
The plasma rifle is an excellent way to conserve ammo for bullet-firing weapons, such as the Uzi or the minigun. It is more powerful as they are against groups of weak or medium-strength enemies, but uses a separate ammo source. This lets the player defeat enemies while preserving bullets for enemies that need a bullet-firing weapon's insta-hit nature to quickly kill them, such as Yagoda the Witch or enemies that are moving around at long range.
The plasma rifle is only ineffective against enemies with an extremely large amount of health, such as the largest version of The General and the Large Spider. The Plasma Rifle doesn't do enough damage per hit to quickly take them down, even though it has a good rate of fire.