<p>Pancreatic cancer is highly malignant, with a five-year overall survival rate of less than 10%. Its diagnosis is often challenging and delayed, and treatment options remain limited. Carbohydrate metabolic reprogramming plays a critical role in pancreatic cancer development, accompanied by the dysregulation of various genes, enzymes, and signaling pathways involved in glycolysis and the pentose phosphate pathway (PPP). These alterations support tumor survival and rapid growth. Targeting these disrupted metabolic pathways with emerging compounds may help overcome chemoresistance and increase senstivity of tumor cells to drugs, making it a promising therapeutic strategy. This review first outlines, the genes and enzymes that are upregulated in glycolysis and PPP in pancreatic ductal adenocarcinoma (PDAC). It then discusses small-molecule drugs and monoclonal antibodies that target these key pathways to control tumor progression. Finally, it examins the connection between carbohydrate metabolic reprogramming and the tumor microenvironment (TME), highlighting its potential role in the development of targeted therapies to improve patient outcomes.</p> Graphical abstract <p></p>