In 1999, Campbell brought Snake out of retirement to infiltrate Zanzibar Land. With Campbell's support over the radio, Snake was able to successfully defeat Zanzibar Land's forces, including the new Metal Gear. The next year, Campbell retired as commander of FOXHOUND.

In 2005, the U.S. government sent Campbell's "niece" Meryl to Shadow Moses island. Soon the island was taken over by members of FOXHOUND, and Campbell was ordered to command the mission to take back the island and rescue the hostages, or else Meryl would be killed. Campbell brought Snake out of retirement to infiltrate the disposal facility. Due to Meryl being held as hostage, Campbell was forced to keep secrets from Snake such as his involvement in the FOXDIE program and what the true purpose of the mission was. Campbell told Snake the truth towards the end of the mission and tried to cancel a nuclear air raid that had been ordered on the base. But before Campbell could make the order, he was arrested by Secretary of Defense, Jim Houseman. Campbell was released after Snake had defeated Liquid Snake, and the Secretary of Defense himself was put under arrest.

Roy Campbell calls Solid Snake back into action in efforts to terminate Liquid Ocelot and destroying Outer Haven. In doing so would destroy the pillar of the world's economy that is based on war.