Abstract: Cellular-Mesenchymal to Epithelial Transition Factor (c-MET), the receptor of hepatocyte growth factor (HGF), is a crucial receptor tyrosine kinase. It plays a vital role in multiple normal physiological processes such as embryonic development and tissue repair. Its aberrant activation participates in the development of various malignancies by regulating pathways including cell proliferation, invasion, and angiogenesis, thus making it an important target for tumor targeted therapy. Although multiple c-MET-targeted drugs have been approved for clinical use, there remains a substantial unmet medical need in clinical practice. This article introduces the molecular structure and signaling pathway of the c-MET, as well as its correlation with tumor progression. It systematically reviews the research history and latest clinical advances in c-MET-targeted drug development, with a focus on summarizing the research status, existing challenges, and progress of various drug categories, including small-molecule inhibitors, monospecific antibodies, bispecific antibodies, and antibody-drug conjugates. This review aims to provide a reference for further research and development of c-MET-targeted therapeutics.