This article reports a case of primary muscle-invasive urothelial carcinoma of the bladder diagnosed in a male patient 9 years after allogeneic kidney transplantation. The patient presented with a one-week history of painless gross hematuria. Computed tomography (CT) and magnetic resonance (MR) imaging revealed a space-occupying lesion at the bladder base and right wall. Pathological examination following transurethral resection of the bladder tumor (TURBT) indicated high-grade invasive urothelial carcinoma. Given the patient's long-term immunosuppressive therapy, multiple comorbidities (particularly severe cardiac dysfunction), and inability to tolerate radical cystectomy or standard chemotherapy, monotherapy with the antibody-drug conjugate (ADC) disitamab vedotin (RC48) was initiated. A multidisciplinary consultation organized by the Guangdong Urological Association concluded that the patient was not a surgical candidate and was unsuitable for combined immunotherapy. It was recommended to switch the immunosuppressive regimen to sirolimus, which has potential antitumor effects, and to perform genetic testing to guide further targeted therapy. After communication with the patient and family, treatment with disitamab vedotin was continued. After the 11th cycle, a second cystoscopy with pathological biopsy of the original tumor site and margins showed no residual carcinoma, indicating a pathological complete response. The treatment was well-tolerated with alopecia as the only notable adverse event. This case suggests that disitamab vedotin monotherapy is a promising and effective option for renal transplant recipients with muscle-invasive bladder cancer who are ineligible for standard treatments due to poor general condition.