Background: Genitourinary (GU) cancers account about 20% of all human cancer in the United States. Tumor lysis syndrome (TLS) is an oncologic emergency with few treatment options. While TLS has been extensively documented in patients with hematological malignancies, it is rarely described in patients with GU cancers. The objective of this study was to investigate the clinical characteristics and outcomes of TLS, a rare but life-threatening complication in GU cancers. Methods: Systematic review of the literature and pooled analysis of published cases of TLS in GU cancers. Results: A total of 180 patients with TLS in solid tumor were included in our study. The median age was 57 years (8-94). Male: female ratio was 1.7. The most common sites were gastrointestinal (29%); followed by genitourinary (22%); lung (16%); melanoma (11%), breast cancer (8.3%). Liver metastasis was documented in 70% of study subjects. TLS occurred as a consequence of cancer therapy in 68% of subjects; and spontaneously in 32% of subjects. Older age and liver metastasis predict high mortality. The clinical features, treatment and outcomes of TLS in 40 cases of GU cancers including testicular germ cell tumor (TGCT) (n=14), renal cell carcinoma (n=10), prostate cancer (n=15), penile cancer (n=1) and urothelial carcinoma (n=3) were compared. The mortality rate of TLS were 50% in TGCT, 70% in renal cell carcinoma, 64% in prostate cancer 67% in urothelial carcinoma. Conclusions: TLS in GU cancers is associated with very high mortality. TLS should be considered on the differential diagnosis, when evaluating renal failure and electrolyte derangement in patients with metastatic GU cancers with liver metastases. The clinical features and outcomes of TLS in genitourinary cancers.