This article reports a case of progression after bladder-preserving multimodal therapy. A 47-year-old man was admitted with a 2-year history of bladder-preserving treatment for muscle-invasive bladder cancer (MIBC). Initial transurethral resection of bladder tumor (TURBt) in August 2022 revealed high-grade invasive urothelial carcinoma with glandular differentiation and invasion of the lamina propria, with immunohistochemistry showing Her-2 (3+) and PD-L1 combined positive score≈10. Owing to his strong preference for bladder preservation, the patient received combination therapy with disitamab vedotin plus toripalimab and underwent repeated TURBt, achieving temporary disease stabilization. In January 2025, imaging studies revealed a progressive lesion in the posterior wall of the urinary bladder with multiple pelvic/retroperitoneal lymph node metastases. Concurrently, pathology results from TURBt confirmed high-grade papillary urothelial carcinoma. Radical resection or systemic chemotherapy was recommended, but the patient refused again. In April 2025, further PET-CT demonstrated multiple enlarged lymph nodes with highly active metabolism adjacent to the left common iliac vessels and internal/external iliac vessels. And then, the patient underwent robot-assisted radical cystectomy with pelvic lymph node dissection and ileal conduit. Pathology revealed urothelial carcinoma with lamina propria invasion and lymph node metastases (ypT₁N₃M₀). Next-generation sequencing identified pathogenic mutations in TP53, EP300, KMT2A, and TERT. Multidisciplinary team discussion concluded that this patient represents a high-risk subgroup requiring multimodal systemic therapy. Given prior immune-related rash, adjuvant immunotherapy was withheld, and the patient instead received concurrent chemoradiotherapy with cisplatin, followed by consolidation chemotherapy with gemcitabine plus cisplatin, achieving stable disease on follow-up. This case highlights that bladder-preserving strategies failing with nodal metastasis warrant salvage radical cystectomy combined with systemic therapy. Early recognition of nodal metastases requires not only conventional imaging size criteria but also morphologic features and integration of molecular diagnostics, which may improve individualized management and long-term outcomes.