This review provides an in-depth examination of the tumor microenvironment, macrophages, and PD-1 checkpoint inhibitors. It delves into the fundamental aspects of the tumor microenvironment and macrophages, discussing the evolution of key concepts, the involvement of macrophages in tumor progression, and their interactions with tumor cells. The historical development of PD-1 checkpoint inhibitors is explored, detailing their discovery, early clinical trials, and initial challenges. Current insights into macrophages within the tumor microenvironment are presented, including their polarization, mechanisms of immunosuppression, and diagnostic techniques. The clinical application of PD-1 inhibitors is reviewed, encompassing therapeutic strategies, comparative efficacy across various cancers, and management of side effects. Additionally, the paper addresses technological advancements in tumor microenvironment research, future directions, and ongoing controversies, aiming to provide a comprehensive overview to inform further research and clinical applications.