Metastatic urothelial carcinoma, the most common subtype of advanced bladder cancer, remains associated with poor outcomes and limited treatment options despite systemic therapies. Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has shown significant improvements in progression-free and overall survival in platinum- and immunotherapy-pretreated patients, as demonstrated in the EV-201 and EV-301 trials. In this report, we present a case of a patient who had previously received platinum-based neoadjuvant chemotherapy and experienced disease progression under nivolumab maintenance therapy but subsequently achieved a complete response in a short period with EV treatment. EV has emerged as a valuable treatment alternative in this aggressive disease, where survival expectations are generally poor. However, questions remain regarding which patients benefit most from the treatment and whether the response is correlated with nectin-4 expression levels.