The combination of antibody–drug conjugates (ADCs) with immunotherapy has delivered major breakthroughs across several tumor types, including urothelial carcinoma. At the 2025 European Society for Medical Oncology (ESMO) Congress, results from a pivotal Phase III trial (LBA7) were presented showing that the HER2-targeted ADC disitamab vedotin, combined with the PD-1 inhibitor toripalimab, nearly doubled overall survival compared with chemotherapy as first-line treatment for patients with HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC). This novel regimen, centered on an innovative ADC, may redefine first-line therapy—though several key questions remain.