Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited therapeutic options and poor prognosis. The combination of immunotherapy and radiotherapy has emerged as a promising strategy to enhance anti-tumor efficacy in various cancers. This review explores the synergistic potential of combining immunotherapy with radiotherapy in PDAC treatment. Immunotherapy, particularly immune checkpoint inhibitors, aims to boost the immune system’s ability to recognize and destroy cancer cells. However, the immunosuppressive tumor microenvironment in PDAC often limits its effectiveness. Radiotherapy, on the other hand, can induce immunogenic cell death and modulate the tumor microenvironment to enhance immune response. We discuss preclinical and clinical evidence supporting the combination approach, including the mechanisms by which radiotherapy can augment immunotherapy efficacy in PDAC. Challenges such as optimal sequencing, dosing, and potential toxicities are also addressed. The integration of immunotherapy and radiotherapy holds significant promise for improving outcomes in PDAC patients, warranting further investigation through clinical trials.