The hepatocyte growth factor/c-mesenchymal-epithelial transition factor (HGF/c-MET) pathway plays a crucial role in cancer biology, rendering it an attractive therapeutic target across multiple malignancies. This study comprehensively reviewed the structure and function of c-MET, its role in tumorigenesis, and its potential as a cancer target. This study also provides an overview of small-molecule inhibitors and monoclonal antibodies targeting the HGF/c-MET axis, their mechanisms of action, and results from clinical trials. Furthermore, we have addressed emerging treatment strategies, including combination therapies with immune checkpoint inhibitors and antibody-drug conjugates. Although challenges in standardizing measurement protocols for HGF/c-MET exist, identifying biomarkers is crucial for planning clinical interventions and categorizing patients, with the ultimate goal of advancing toward individualized medical care. Future studies should focus on optimizing current c-MET inhibitors, improving patient selection, overcoming drug resistance, and developing more efficacious treatment strategies for c-MET-dependent malignancies.