Abstract: Nectin cell adhesion molecule 4 (Nectin-4) is a calcium-independent immunoglobulin-like cell adhesion molecule that is expressed at low levels in normal adult tissues but is overexpressed in multiple solid malignancies, including lung cancer, breast cancer, urothelial carcinoma, bladder cancer, gastric cancer, and pancreatic cancer. It promotes tumor cell proliferation, distant metastasis, angiogenesis, cell-cell and cell-matrix adhesion, post-treatment local and distant recurrence, and DNA mismatch repair, thereby contributing to poor prognosis. As a powerful tool, molecular imaging technology enables the direct characterization and quantification of molecular metabolic changes upon probe-target binding in vivo. It has become a key approach for investigating Nectin-4, playing an important role in target-specific diagnosis, tumor staging, and therapeutic response monitoring. Various Nectin-4-targeted molecular probes based on monoclonal antibodies, antibody-drug conjugates, nanobody-drug conjugates, and bicyclic peptides have been evaluated in preclinical and clinical studies across multiple solid tumors. The authors summarize the latest advances in tumor molecular imaging technologies targeting Nectin-4.