The Mesa Lab was an early laboratory of Dr. Wily, built inside a desert mesa, where he worked on various robotics projects. His most infamous project was the Wily Walker, a mobile weapons platform equipped with highly advanced armaments, including chemical weapons. Upon learning that the Walker was equipped with these, the government sanctioned Dr. Wily, imposing a ban on future work in robotics. The Mesa Lab was condemned and abandoned, but due to the chemical weapons contained within, it was deemed too dangerous to disassemble.
Many years later, after Dr. Wily's second set of Robot Masters stole the Energy Elements intended to power Gamma, he suggested that they might have taken refuge in the Mesa Lab due to Ra Moon having access to his old files. Mega Man, Bright Man, and Pharaoh Man were sent there by Dr. Light and Dr. Cossack to investigate, and after overcoming some of the bases still-functioning defenses ran into the Wily Walker. Dr. Wily transmitted a code to the trio to deactivate the immobile walker; in reality, the code was meant to activate the machine in the hopes that it would destroy the Robot Master trio. After Mega Man survived nearly being crushed by the giant machine, they managed to trap it inside the lab, but were left unsure how to deactivate it. Eventually, as a last resort, Dr. Wily and Dr. Cossack (the latter with extreme reluctance), modified Bright Man's light source to act as a special weapon via Mega Man, succeeding in disabling the Wily Walker, although Pharaoh Man was damaged in the process requiring maintenance. Despite Dr. Wily's failure to destroy them with the Wily Walker, Wily was relatively unphased, as he knew that he won either way due it still buying enough time for the third generation Robot Masters to get into position as well as completing his third castle, plus completing Doc Robot to use against Mega Man, although the quickness in how they tracked down half of the Robot Masters had him realize that he needed to accelerate his plans.
Over 100 years later, the Mesa Lab was discovered by Dr. Cain's archaeology team, who set about excavating the site. Mega Man X joined him there, only for the Walker to once again be set in motion. The dangerous construct soon escaped the Mesa Lab, forcing the Maverick Hunters-including Zero and Vile-to join X in his efforts to halt the monstrous machine.