Pancreatic ductal adenocarcinoma (PDAC) is a common cause of cancer-related death, and most patients are with advanced disease when diagnosed. At present, despite a variety of treatments have been devel- oped for PDAC, few effective treatment options are available; on the other hand, PDAC shows significant resistance to chemoradiotherapy, targeted therapy, and immunotherapy due to its heterogeneous genetic profile, molecular signaling pathways, and complex tumor immune microenvironment. Nevertheless, over the past decades, there have been many new advances in the key theory and understanding of the in- trinsic mechanisms and complexity of molecular biology and molecular immunology in pancreatic can- cer, based on which more and more diverse new means and reasonable combination strategies for PDAC treatment have been developed and preliminary breakthroughs have been made. With the continuous ex- ploration, from surgical local treatment to comprehensive medical management, the research-diagnosis- management system of pancreatic cancer is improving. This review focused on the variety of treatments for advanced PDAC, including traditional chemotherapy, targeted therapy, immunotherapy, microenviron- ment matrix regulation as well as the treatment targeting epigenetics, metabolism and cancer stem cells. We pointed out the current research bottlenecks and future exploration directions.