This review systematically summarized the key molecular and cellular mechanisms of neural-immune-cancer interactions in pancreatic cancer and specifically discussed several translational strategies, including neurotrophic factor blockade targeting NGF/TrkA and GDNF/RET, myeloid cell reprogramming targeting CXCR2/CXCL to improve T cell infiltration, and potential combination strategies that combine neuromodulatory drugs (e.g., β-blockers or CRGP antagonists) with immune checkpoint inhibitors. This evidence concerns the gene GDNF and cancer.