Mega Man IV follows the general pattern of previous Game Boy titles, combining content from existing NES titles with unique content and features. As with the previous Game Boy entries, the Robot Masters are taken from two different NES titles, with the first four taken from Mega Man 4, while the latter four come from Mega Man 5. Also following this pattern, the first four Robot Masters must be defeated before the second set of four can be accessed. Beat also appears, able to be called for assistance once Mega Man has obtained the B, E, A, and T plates found in the levels of the first four Robot Masters. Stages can be revisited after the Robot Master has been defeated, allowing Mega Man to collect items found in the stage, including key items such as plates.
Mega Man IV introduces elements from the NES series of games which previously had not been seen on the Game Boy. Most prominently, this includes the Boss Rush. Mega Man IV also includes the Energy Balancer, an item first seen in Mega Man 6.
Additionally, Mega Man IV adds a number of new features not seen in any previous titles, Game Boy or NES. The stage select screens have been changed from the typical grid layout to a top-down rotating view, with the bottom portion of the screen reserved for showing stylized artwork depicting the selected Robot Master and their stage. Several new collectable items have been added, specifically Weapon (W) Tanks, Super (S) Tanks, and Mini Energy Tanks, four of the latter combining to form one traditional Energy Tank. The New Mega Buster now has a small amount of kickback when fully charged, pushing Mega Man a small distance in the direction opposite where he is aiming. While Mega Man's health is automatically restored between levels, special weapon energy is not, though it can be done at Dr. Light's Lab between levels in exchange for P Chips.
Perhaps the most noticeable new feature in the game is the introduction of P Chips, the earliest version of what would later become Screws in Mega Man 7. Appearing as cylindrical capsules bearing the letter P, P Chips can be found throughout the game, either placed in the level or randomly dropped when an enemy is destroyed. P Chips have no immediate function when collected, but are used after completion of a level, when Mega Man is given the opportunity to travel to Dr. Light's Lab. There, P Chips can be used by Dr. Light to replicate items of Mega Man's choosing, including 1-UPs, various Tanks, the Energy Balancer, and an immediate recharge of all of Mega Man's special weapons.
Sometime after Mega Man 5, Dr. Wily attends the annual Robot Masters Exposition where he manages to reprogram some of the Robot Masters that were on display. Although Dr. Light and Mega Man were also in attendance, Wily failed to reprogram Mega Man. Thus, Dr. Light sends Mega Man out to stop Wily before he can use his newly reprogrammed robots to wreak havoc across the globe. Mega Man manages to defeat the first four Robot Masters and make his way to Wily's fortress, where he encounters a new Mega Man Killer named Ballade, and although he defeats him, Ballade promptly leaves, opening the way up to where four more Robot Masters lay in waiting. However, after Mega Man defeated them, he made his way to where Ballade was waiting and defeated him for a second time, acquiring the Ballade Cracker, which he used to blast his way out of Wily's crumbling fortress. Mega Man made his way to Wily's new space fortress and defeated Wily, but was trapped in the fortress when Wily activated a self-destruct mechanism. However, Ballade had a sense of self-sacrifice at the last minute and saved Mega Man in the end.