Abstract: C-C chemokine ligand 2 (CCL2) and its receptor CCR2 are involved in the initiation and progression of various cancers, and have become a research hotspot in tumor immunotherapy. In the tumor microenvironment, activation of the CCL2-CCR2 axis not only promotes the migration of immunosuppressive macrophages but also exacerbates cancer progression through multiple mechanisms such as enhancing tumor cell proliferation and invasion, inducing angiogenesis, and recruiting immunosuppressive cells to promote tumor initiation, development, and immune evasion. Clinical trials targeting the CCL2-CCR2 signaling pathway in solid tumors and metastatic cancers have further validated its critical role in cancer progression. This review summarizes the structure and function of the CCL2-CCR2 axis, its role in the tumor microenvironment and cancer progression, and discusses current preclinical and clinical research on targeted therapies against the CCL2-CCR2 axis, aiming to provide some insights for the development of CCL2/CCR2 inhibitors for cancer treatment.