Abstract: Tumor-associated macrophages (TAMs), the most abundant innate immune population in the tumor microenvironment and the main driving force in the formation of immunosuppressive microenvironment, play a crucial role in tumor immune escape. Therefore, targeted regulation of TAMs has become a new strategy for cancer immunotherapy. Recent studies have found that a variety of signaling pathways play an important role in regulating the function of TAMs. Small molecule drugs targeting these signaling pathways can exert anti-tumor effects by regulating TAMs, and many of them are in different clinical trial phases. This paper systematically reviews the signaling pathways regulating the function of TAMs as well as the development process and binding mode of related small molecule inhibitors in order to provide some insight for the development of small molecule drugs regulating TAMs.