Objective: To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer (MIBC) with intermediate-to-high-risk primary prostate cancer. Methods: From January 2012 to October 2023, the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed. All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study. Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients. For significant influencing factors (pathological T stage, M stage and perineural invasion of bladder cancer), survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors. Results: A total of 32 patients were included in this study. The mean age was (72.5±6.6) years; the median preoperative total prostate specific antigen (tPSA) was 6.68 (2.47, 6.84) μg/L; the mean preoperative creatinine was (95±36) μmol/L, and the median survival time was 65 months. The majority of the patients (87.5%) had high-grade bladder cancer, 53.1% had lymphatic invasion, and 31.3% had perineural invasion. Prostate involvement was observed in 25.0% of the cases, and the positive rate of soft-tissue surgical margin was 37.5%. Multivariate Cox analysis revealed that preoperative creatinine level (HR=1.02, 95%CI: 1.01-1.04), pathological stage of bladder cancer T3 (HR=11.58, 95%CI: 1.38-97.36) and T4 (HR=19.53, 95%CI: 4.26-89.52) metastasis of bladder cancer (HR=9.44, 95%CI: 1.26-70.49) and perineural invasion of bladder cancer (HR=6.26, 95%CI: 1.39-28.27) were independent prognostic factors (P < 0.05). Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3, T4, M1, and perineural invasion were unfavorable factors affecting the patients' survival prognosis (P < 0.05). Conclusion: Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis. High preoperative serum creatinine, T3 or T4 pathological stage of bladder cancer, metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.