ObjectiveTo systematically review the evidence evolution of neoadjuvant, adjuvant, and perioperative comprehensive treatment strategies for resectable pancreatic ductal adenocarcinoma (PDAC), analyze the efficacy and limitations of different therapeutic modalities, and propose future directions to guide clinical practice. MethodsA systematic review and analysis were conducted of pivotal randomized controlled trials and landmark studies regarding resectable PDAC published over the past three decades. Three core strategies, including adjuvant chemoradiotherapy, adjuvant chemotherapy, and combined neoadjuvant-adjuvant therapy, were focused on. The study designs, endpoints, and key conclusions of representative trials were subsequently summarized. ResultsAdjuvant chemoradiotherapy has been progressively marginalized, as no overall survival benefit has been confirmed and increased toxicities have been observed in most randomized controlled trials; its use is currently restricted to highly selected patients. In contrast, adjuvant chemotherapy has emerged as the cornerstone of care, with iterative refinements in regimens—from single-agent gemcitabine to gemcitabine plus capecitabine, S-1 monotherapy (for Asian populations), and mFOLFIRINOX (for appropriately selected patients)—resulting in significantly prolonged survival. Combined neoadjuvant-adjuvant therapy has emerged as a prominent focus, with multiple phase Ⅱ/Ⅲ trials demonstrating improved R0 resection rate, disease-free survival, and overall survival with multidrug regimens such as mFOLFIRINOX. However, these benefits are found to be highly dependent on chemotherapy intensity, patient tolerance, and surgical quality. Additionally, both immunochemotherapy and circulating tumor DNA-based minimal residual disease surveillance are under active investigation as promising therapeutic and monitoring strategies, respectively.ConclusionsThe perioperative management of resectable PDAC has undergone a paradigm shift—from adjuvant chemoradiotherapy to a systemic, chemotherapy-dominant approach—exemplified by mFOLFIRINOX. Adjuvant chemotherapy is firmly established as the cornerstone of care, reflecting iterative refinement of systemic therapies. While combined neoadjuvant-adjuvant therapy improves R0 resection rate and survival, it requires careful balancing of regimen intensity with patient tolerance. Future development will focus on individualized, whole-course management, integrating immunochemotherapy and circulating tumor DNA-based minimal residual disease surveillance.