Background: The opioid crisis is a growing public health concern in the United States. In this retrospective study, we aim to look at the trends and predictors of opioid overdose-related mortality in cancer patients. Methods: A retrospective analysis of the National Inpatient Sample database (NIS) from 2016 to 2020 was conducted using International Classification of Diseases-10(ICD-10) codes to identify hospitalizations related to opioid overdose. The 2016-2020 mark was chosen because 2016 is the first NIS year with full implementation of ICD-10 code and there is absence of data after 2020. STATA version SE18.0 was used for statistical analysis. We used multivariate regression analysis to calculate the effects of various demographic and non-demographic variables including age, sex, Charlson Comorbidity Index(CCI), race, median household income, type of insurance, hospital bed size, hospital region, chronic lung disease, neuromuscular disease, and alcohol use disorder on opioid overdose-related mortality. Results: There were 6980 hospitalizations with opioid overdose in cancer patients. Mean age was 62.3 years and 49.9% were females. 97.9% of patients had high CCI. The trend of opioid overdose-related mortality in cancer patients is shown in the table. Unlike increasing opioid overdose related mortality in the general population (which, per CDC, increased by 62.44% from 2016 to 2020), we found that opioid-related admissions and mortality in cancer patients are stable over five years. Significant predictors of mortality (p-value <0.05) included male sex, African-American race, lower-median household income, and chronic lung disease with the odds ratio 1.64, 2.62, 2.13, and 1.69 respectively. Conclusions: The ongoing opioid crisis has led to tighter regulations regarding opioid prescriptions, subsequently creating increasing obstacles for cancer patients to access opioids. This analysis indicates that hospitalizations and deaths related to opioids in cancer patients have remained relatively stable, in contrast to the general population. Therefore, it is crucial to establish distinct regulations for cancer patients compared to the general population to ensure appropriate access to opioids for effective pain management. In addition, this study identified key predictors of mortality from opioid overdose in cancer patients, highlighting the complex interplay of socio-economic factors in medical care. The limitations of this study include multivariate model’s inability to account for all variables, coding errors, and an increased risk of bias due to the retrospective nature of the data.