Introduction: Urothelial carcinoma can arise from the urinary bladder or from the upper urinary tract. In some instances, urinary bladder cancer (UBC) and upper tract urothelial carcinoma (UTUC) can be concurrently diagnosed, necessitating a combined radical cystectomy (RC) with radical nephroureterectomy (RNU). A systematic review was done on the combined procedure exploring outcomes and indications, in addition to a comparative analysis between the combined procedure and cystectomy alone. Methods: For the systematic review, three databases (Embase, PubMed, and Cochrane) were queried, selecting only studies that included intraoperative and perioperative data. For the comparative analysis, using the NSQIP database, CPT codes for RC and RNU were used to identify two cohorts, one with RC and RNU and one with RC alone. A descriptive analysis was performed on all preoperative variables, and propensity score matching (PSM) was performed. Postoperative events were then compared between the two matched cohorts. Results: For the systematic review, 28 relevant articles were included amounting to 947 patients who underwent the combined procedure. The most common indication was synchronous multifocal disease, the most common approach was open surgery, and the most common diversion technique was using an ileal conduit. Almost 28% of patients required blood transfusion and remained in the hospital for an average of 13 days. The most common postoperative complication was prolonged paralytic ileus. For the comparative analysis, 11,759 patients were included of which 97.5% underwent RC only and 2.5% underwent the combined procedure. After PSM, the cohort that had undergone the combined procedure showed an increased risk of renal injury, increased readmission rates, and increased reoperation rates. Whereas the cohort that had undergone RC only showed an increased risk of deep venous thrombosis (DVT), sepsis, or septic shock. Conclusion: A combined RC and RNU is a treatment option for concurrent UCB and UTUC that should be cautiously utilized as it is associated with high morbidity and mortality. Patient selection, discussion of the risks and benefits of the procedure, and explanation of the available treatment options remain the most important pillars in managing patients with this complex disease.