Background: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Patients with a rapidly proliferating tumor or high tumor burden after cytotoxic chemotherapy, predominantly in hematologic malignancies, are at increased risk of TLS. The advancement in therapeutic strategies of oncology in the past few decades has expanded the spectrum of malignancies associated with TLS. A dearth of literature on the incidence of TLS in various solid malignancies exists. Using the National Inpatient Sample (NIS) data, this study aims to highlight the solid malignancies at risk of TLS, highlight the demographic factors, and draw a comparison with that in hematological malignancies. Methods: The NIS 2016-2019 dataset was analyzed utilizing univariate and multivariate logistic regression analysis for the predictors of TLS (P <0.05). StataCorp. 2021. Release 17. College Station, TX: StataCorp LLC, BE version with Stata’s svy command, and appropriate weights, were used to perform the analysis. The overall fit was analyzed using Receiver Operative Curves (ROC), and sensitivity analysis was analyzed using the e-value package. Results: From 2016-2019, a total of 51,385 (48,917-53,853) hospitalizations had an incidence of TLS. We included 16,249 cases of TLS in patients treated for the ten most common malignancies in the US. We found that older age, male sex, and black race were associated with higher odds of TLS. It was reported highest in large hospitals and urban non-teaching hospitals. The regional distribution of the TLS suggests the highest odds in the Western region. The odds of getting TLS were highest among Leukemias and Lymphomas, respectively. Among solid tumors, the odds of getting TLS were highest in uterine cancer patients, followed by lung, breast, pancreatic, and liver cancer among the top five. (Table). Conclusions: In this study, we conclude that solid tumors, mainly uterine, followed by lung and breast, have significantly higher odds of TLS, more so in larger or non-teaching hospitals. There is a need to establish specific management guidelines to prevent these TLS cases that will improve the morbidity and mortality associated with TLS and help build more cost-effective treatment regimens.