Oncolytic viruses are a class of viruses that are naturally or genetically engineered to replicate specifically in tumor cells and exert anti-tumor effects. The anti-tumor effect of oncolytic virus is mainly achieved through the following two aspects: (1) direct oncolytic effect, such as inducing apoptosis of tumor cells and promoting cell lysis; (2) as a drug that activates immunity, oncolytic viruses induce the body to produce strong anti-tumor immunity and achieve the purpose of clearing tumors. As an important branch of immunotherapy, oncolytic viral therapy has become a research hotspot in this field due to its tumor specificity and convenient genetic modification. Until now, only four products have been approved for marketing, despite more than 100 cases of oncolytic viral therapies in the recruitment and completion stages of clinical trials. There continue to be many challenges in the application of oncolytic therapy in oncology treatment. Therefore, a systematic review of oncolytic virus modification strategies and an in-depth understanding of the biological processes of oncolytic viruses are all the more necessary. Viruses are host-dependent in their replication and proliferation processes, and their biological processes are closely related to the metabolic state of the host. The hallmark feature of tumors is metabolic reprogramming, the process by which tumor cells reconsider their metabolic networks to meet the demands of exponential growth and proliferation and to prevent oxidative stress. This typically includes enhanced glycolysis and glutaminolysis, as well as changes in mitochondrial function and redox homeostasis.The replication of oncolytic viruses requires the synthesis of biological macromolecules, such as amino acids, lipids, nucleotides, etc. Viruses themselves do not encode relevant enzymes, so they often need to use the metabolic pathways of their host cells to synthesize the substances they need. Enhancing the replication and oncolytic ability of oncolytic viruses by targeting host metabolic reprogramming is a promising direction. It has been shown that lipid metabolism and intermediates are one of the ways in which viruses engage in dialogue with their hosts, and lipid rafts are essential components for oncolytic viruses to perform their infection and replication functions. Cholesterol depletion in host cells has shown conflicting results, presumably related to the type of virus. For example, the dependence of envelope and non-envelope viruses on lipid synthesis may differ, although this needs more literature support. The idea that enhanced glycolytic levels in host cells promote the infection, replication, and anti-tumor effects of oncolytic viruses is equally controversial. Oncolytic viruses replicate to a degree comparable to that of proliferative tumor cells, and both rely on glutamine metabolism to participate in the synthesis of biological macromolecules. Adenoviruses and VSV are significantly less able to replicate in states where the glutamine metabolic pathway is suppressed. Similarly, the level of host nucleotide metabolism is closely related to the replication capacity of oncolytic viruses, and enhancing RNA reductase (RR) activity can promote HSV replication in tumors. Therefore, the use of oncolytic viruses to regulate host metabolic reprogramming, or in combination with drugs that can regulate host metabolism, is one of the directions to further improve oncolytic virus anti-tumor efficacy.