Abstract: Metastatic urothelial carcinoma (mUC) is a malignancy with poor prognosis. Conventional treatments such as platinum-based chemotherapy and immune checkpoint inhibitors have achieved relatively limited efficacy and poor survival outcomes, and resistance is frequently observed. In recent years, enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has demonstrated significant clinical benefits for patients with mUC. Here, we review the evidence for the clinical use of EV and summarize its mechanism, pharmacological properties, as well as the efficacy and safety of EV monotherapy in patients with mUC whose cancer has progressed after first-line therapy. Furthermore, we present analyses of clinical data and describe synergistic mechanisms of EV combined with pembrolizumab ( EV+P regimen) as a first-line treatment. We also discuss its performance in specific populations and real-world clinical practice, summarize guidelines for adverse event management, as well as recommendations from both domestic and international guidelines, for the purpose of expanding treatment options for mUC.