Nectin-4 is a cell adhesion molecule which has gained more and more attention as a therapeutic target in cancer recently. Overexpression of Nectin-4 has been observed in various tumors, including breast cancer, and is associated with tumor progression. Enfortumab vedotin(EV)is an antibody-drug conjugate (ADC) targeting Nectin-4, which has been approved by FDA for the treatment of urothelial carcinoma. Notably, Nectin-4 was also investigated as a target for breast cancer in preclinical and clinical settings. Nectin-4-targeted approaches, such as ADCs, oncolytic viruses, photothermal therapy and immunotherapy, have shown promising results in early-phase clinical trials. These therapies offer novel strategies for delivering targeted treatments to Nectin-4-expressing cancer cells, enhancing treatment efficacy and minimizing off-target effects. In conclusion, this review aims to provide an overview of the latest advances in understanding the role of Nectin-4 in breast cancer and discuss the future development prospects of Nectin-4 targeted agents.