<p>Upper tract urothelial carcinoma (UTUC) is a relatively uncommon malignancy, and radical nephroureterectomy (RNU) is the standard treatment for high-risk disease. However, management becomes challenging in patients with a solitary kidney, as radical surgery may result in dialysis dependence. Recently, enfortumab vedotin combined with pembrolizumab has shown promising efficacy in advanced urothelial carcinoma. A 74-year-old man with a history of right radical nephroureterectomy for UTUC developed a tumor in the contralateral ureter accompanied by progressive renal dysfunction. Ureteroscopic biopsy demonstrated low-grade non-invasive urothelial carcinoma, however, imaging and endoscopic findings raised suspicion of clinically invasive disease (suspected cT2N0M0). Because radical surgery would likely have resulted in dialysis dependence, treatment selection was challenging. A ureteral stent was placed to relieve obstruction, and systemic therapy with enfortumab vedotin plus pembrolizumab was initiated after multidisciplinary discussion and detailed informed consent. After ten cycles of therapy, radiologic and endoscopic findings demonstrated marked tumor regression, and ureteroscopic biopsy revealed no definite residual malignancy. The ureteral stent was subsequently removed, and renal function remained stable. The patient has since remained free of disease progression without additional treatment during follow-up. We report a clinically challenging case of contralateral ureteral tumor in a solitary kidney that showed a favorable clinical course following treatment with enfortumab vedotin plus pembrolizumab. This case highlights the importance of individualized multidisciplinary decision-making in complex clinical situations.</p>