Tumor drug resistance is the main cause of clinical treatment failure. According to conventional wisdom, resistance is mostly caused by greater drug efflux, accelerated DNA repair, and decreased apoptosis. In recent years, more and more studies have shown that glucose metabolic reprogramming, as a key mechanism for tumor cells to adapt to the unique tumor microenvironment and obtain the advantages of survival and proliferation, also plays a very important role in regulating the process of tumor drug resistance. In addition to providing sustained material and energy supplies for their own rapid growth and proliferation, the abnormally active aerobic glycolysis and pentose phosphate pathway in tumor cells can also affect drug tolerance through pathways like regulating redox homeostasis, enhancing cellular stemness, and reshaping the tumor microenvironment. Additionally, the combination treatments that target glycose metabolic reprogramming combined with anticancer medications have shown progressively greater therapeutic benefits. This article reviews the research progress of glucose metabolic reprogramming in the resistance to various anti-tumor drugs, in order to provide a new breakthrough for the increasingly prominent status quo of tumor cell drug resistance.