Bacterial dysbiosis is evolving as an advocate for carcinogenesis and has been associated with pancreatic cancer progression and survival outcomes. The gut and pancreas of cancer patients harbor a unique microbiome that differs significantly from that of healthy individuals. We believe that the pancreatic cancer microbiome regulates tumorigenesis by altering host cell function and modulating immune cells, skewing them toward an immunosuppressive phenotype. Moreover, altering this pathogenic microbiome may enhance the efficacy of current therapies in pancreatic cancer and improve survival outcomes. This review highlights the findings on microbial modulation across various pre-clinical and clinical studies and provides insight into the potential of targeting the microbiome for pancreatic cancer therapy.