Tumor lysis syndrome (TLS) remains a debilitating cause of hospitalization and death in patients with cancer and is a significant challenge for healthcare providers despite advancements in its management. This umbrella review analyzed the results of meta-analyses on the use of rasburicase in the treatment of patients with cancer. A literature search was performed of five databases (PubMed, Google Scholar, Cochrane Library, Scopus, Global Index Medicus, and ScienceDirect) for articles with full texts available online. A measurement tool to assess systematic reviews 2 (AMSTAR 2) was used to assess the quality of the included studies, and Review Manager software was used to conduct all statistical analyses. The systematic search identified eight relevant meta-analyses, with primary analyses including outcome data that analyzed mortality, renal failure, and comparisons with allopurinol. The pooled data showed that rasburicase effectively reduced TLS development and serum uric acid levels in children and adults with malignancies. Most outcomes did not differ significantly compared with those of allopurinol. Future trials should focus on the cost-effectiveness of rasburicase compared to that of allopurinol while including high-, intermediate-, and low-risk patients. Rasburicase is safe and effective for managing patients with TLS. However, recent large-scale meta-analyses have reported conflicting results. Most meta-analyses were graded as low to critically low as per AMSTAR 2. The analysis revealed that the benefit of rasburicase did not differ significantly from that of allopurinol, which has higher cost-effectiveness and fewer side effects.