The Me 410 B was planned to be fitted with the DB 603G engine and a few other improvements. However, due to the shortage of the new engine, early production of the Me 410 B instead utilized the regular DB 603A found in the Me 410 A. Some Me 410 B's received an oxygen system for high-altitude flights as well as a better undercarriage. The Me 410 B-2/U4 Zerstörer (Destroyer in German) was fitted with a 5 cm cannon mounted in the chin of the nose. Around 130 planes of this variant were produced, 80 built at Messerschmitt's factory and the rest built at Dornier's factory. In addition to the giant cannon, it also had two 20 mm MG 151 cannons as part of the Waffenbehӓlter conversion set.

In the game since the start of the Open Beta Test prior to Update 1.27, the Me 410 B-2/U4 is a fairly decent ground attacker. The BK 5 cannon has access to both HVAP and AP shells, the latter being extremely effective from top down into tanks. The B-2/U4 variant also has two 20 mm MG 151 cannons mounted in the nose which complements the main cannon. For defense, the Me 410 B has two single 13 mm turrets, one mounted on each side of the fuselage. All around, the Me 410 B-2/U4 has a fairly decent set of guns but does lack bombs and rockets.