Urothelial carcinoma (UC) is a highly lethal malignancy in the metastatic state. Platinum-based chemotherapy regimens have been the backbone treatment for patients with advanced UC in the first-line setting. However, a large subset of patients are suboptimal candidates for these combinations owing to poor renal function and/or other comorbidities. Patients who are unable to tolerate or who progress after frontline platinum chemotherapy face a poor outcome. Recent insights into UC biology and immunology are being translated into new therapies for metastatic UC (mUC) including immune checkpoint inhibitors (ICIs), erdafitinib, a FGFR inhibitor, and antibody drug conjugates (ADC) such enfortumab vedotin.