When a new disease called the Bugster Virus or "Game disease" begins infecting people across japan, the ministry of health works with GEMM Corp., a major video game company, to create the Cyber Rescue Center or "CR" and recruit a group of Doctor Riders including Emu Hojo AKA Kamen Rider Ex-aid, a medical intern with incredible gaming skills, and Hiiro Kagami AKA Kamen Rider Brave, a young genius surgeon who has never had a failed operation. Together with the help of Poppy Pipopapo, a Bugster reprogrammed to help them, they set out to cure the japan of the Bugster Virus. But they soon find that they aren't the only Doctor Riders out there and that the CEO of GEMM Corp. has his own motives in all this that could threaten their mission.