Pancreatic ductal adenocarcinoma (PDAC) is a global health challenge and remains one of the most lethal malignancies; there are only a few therapeutic options. However, significant efforts have led to the identification of major genetic factors that drive the progression and pathogenesis of PDAC. Notably, the research and application of molecular targeted therapies and immunotherapies have rapidly increased and facilitated great progress in the treatment of many malignant tumors, additional targeted therapies and immunotherapy based on next-generation sequencing results provide new opportunities for the diagnosis and treatment of pancreatic tumors. Immune checkpoint inhibitors are also now being incorporated as PDAC therapies, and combinations of molecularly targeted therapies with immunotherapies are emerging as strategies for boosting the immune response. The investigation of biomarkers of a response or primary resistance to immunotherapies is also an emerging research area. Herein, we further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies. We presume that the clinical translation of these research efforts will improve the survival outcomes of this challenging disease, which are currently dismal.