Objective <p>The existing literature on the direct effects of opioid use on cancer is limited. The goal of our systematic review and meta-analysis is to consolidate the findings of previous studies and provide a pooled effect size regarding the association between opioid usage and cancer.</p> Methods <p>The PRISMA guidelines were employed to construct a framework for conducting this systematic review and meta-analysis. A systematic search was conducted in international and national databases. A search of PubMed, Web of Science, Scopus, and national electronic databases was conducted up to May 2024. The random effects model was employed for the presentation of results with a 95% confidence interval. The statistical analysis was conducted using Stata 11.</p> Results <p>Out of 1674 articles were retrieved 38 studies remained in the final analysis (six cohort study and 32 case-control studies). The pooled adjusted odds ratio of opium on esophageal cancer was 1.68 (95% CI: 1.36, 2.08), for bladder cancer was 5.00(95% CI: 3.76, 6.66), for head and neck cancer was 4.93 (95% CI: 2.41, 10.06) for pancreatic cancer was 2.4 (95% CI: 1.62, 2.56) for lung cancer was 2.89(95% CI: 2.14, 3.30) for laryngeal cancer was 6.76 (95% CI: 3.77, 11.80) for gastric cancer was 3.13 (95% CI: 1.92, 5.11) and for colorectal cancer was 2.51 (95% CI: 1.04, 6.07).All association were statistically significant.</p> Conclusion <p>The findings underscore the potential carcinogenic effects of opium on cancers. Public health organizations should work collaboratively to mitigate opioid exposure while promoting alternative pain management strategies to protect community health and reduce the burden of cancer.</p>