Background <p>Urothelial carcinoma (UC) represents a&#xa0;significant global health burden and its incidence is consistently increasing worldwide. Treatment options for advanced or metastatic UC (mUC) have evolved, but extending overall survival (OS) remains a&#xa0;major challenge.</p> Methods <p>This article is based on the content of recent guidelines and a&#xa0;selective literature search.</p> Results <p>In the past, cisplatin-based chemotherapy was the standard first-line treatment for suitable patients for many years. More recently, the introduction of antibody–drug conjugates (ADCs) has added to the medical armamentarium for mUC patients and have been further explored in the form of combination treatments. The combination of enfortumab vedotin (EV) and pembrolizumab (Pem) was clearly superior to standard platinum-based chemotherapy, which permanently changed the medical treatment landscape for mUC. Today, EV plus Pem is the first-line standard of care for the treatment of therapeutically advanced or mUC. In addition, there are new options, such as erdafitinib, which target the fibroblast growth factor receptor (FGFR). In the future, targeted therapy could also be used in the perioperative setting.</p> Conclusion <p>The combination of EV plus Pem is the new standard of care for medical treatment of mUC patients. Erdafitinib is also established in the therapeutic landscape of mUC. Additional studies could help to further improve clinical results.</p>