Locally advanced or metastatic urothelial carcinoma (UC) is a highly malignant disease with a five‑year survival rate of only 5%. In Taiwan, about 40% of UC patients suffer from upper urinary tract urothelial carcinoma (UTUC), which carries a poorer prognosis. Taiwan has the highest incidence of UTUC worldwide. Current treatments include platinum‑based chemotherapy, PD‑(L)1 inhibitors, and Erdafitinib, but all face major limitations. Cisplatin shows only ~50% response, with half of patients intolerant. PD‑(L)1 inhibitors achieve just 10–30% response. Erdafitinib applies to only 6.6% of patients with FGFR2/3 mutations. These gaps highlight urgent unmet needs. PADCEV (Enfortumab Vedotin) is an antibody‑drug conjugate (ADC) targeting Nectin‑4, delivering cytotoxic agents directly to cancer cells. It demonstrates breakthrough activity and provides effective second‑ and later‑line treatment options for patients with advanced UC. PADCEV received accelerated FDA approval in 2019 and is strongly recommended by NCCN (Category 1) and ESMO guidelines for patients previously treated with PD‑(L)1 inhibitors and platinum drugs. Clinical trial results, including EV‑301 (NEJM) and EV‑201 Cohort 2 (Lancet Oncology), confirm its efficacy and high research quality.