Background: Pancreatic cancer is an aggressive malignancy with a dismal 5-year survival rate of only 9%. Novel biomarkers are urgently needed to improve the survival outcomes of patients with this dreaded disease. Cytokines serve a key role in tumor development and metastasis in pancreatic cancer, with each cytokine demonstrating unique functionality in the tumor microenvironment. This meta-analysis examined the role of cytokines in prognosticating overall survival (OS) of pancreatic cancer patients. Methods: Relevant literature were identified via electronic search of PubMed, EMBASE, Google Scholar and Cochrane Library databases up to January 1, 2020. Employing Review Manager 5.3, pooled hazard ratios and 95% confidence intervals were computed. Results: A total of 18 studies comprising 1920 patients were included. Pooled analysis showed worse OS among patients with high T-helper 1 (Th1) cytokines, with a hazard ratio of 1.48 (95% CI 1.27-1.74, p < 0.00001). High T-helper 2 (Th2) cytokines also demonstrated significant association with poor OS, with a hazard ratio of 1.62 (95% CI 1.12–2.34, p = 0.01). In terms of individual cytokines, high IL-6 correlated with inferior OS, with a hazard ratio of 2.73 (95% CI 2.18-3.43, p < 0.00001). Similarly, high IL-12 were linked with worse OS, with a hazard ratio of 1.85 (95% CI 1.26-2.72, p = 0.002). Other individual cytokines were not significantly associated with OS. Conclusions: Cytokines show promise as a prognostic biomarker in pancreatic cancer. Th1 and Th2 cytokines portend worse overall survival outcomes. In particular, high levels of IL-6 and IL-12 can potentially prognosticate patients with poor overall survival. Further prospective studies are encouraged to delineate the role of cytokines in mediating treatment outcomes in this deadly disease.