Abstract Glioblastoma is a highly malignant tumor of the central nervous system with a high mortality rate. The mechanisms driving glioblastoma onset and progression are complex, posing substantial challenges for developing precise therapeutic interventions to improve patient survival. Over a century ago, the discovery of the Warburg effect underscored the importance of abnormal glycolysis in tumors, marking a pivotal moment in cancer research. Subsequent studies have identified mitochondrial energy conversion as a fundamental driver of tumor growth. Recently, lipid metabolism has emerged as a critical factor in cancer cell survival, providing an alternative energy source. Research has shown that lipid metabolism is reprogrammed in glioblastoma, playing a vital role in shaping the biological behavior of tumor cells. In this review, we aim to elucidate the impact of lipid metabolism on glioblastoma tumorigenesis and explore potential therapeutic targets. Additionally, we provide insights into the regulatory mechanisms that govern lipid metabolism, emphasizing the critical roles of key genes and regulators involved in this essential metabolic process.