<p>Glioma is the most common primary malignant brain tumor in adults, among which glioblastoma (GBM) shows the highest degree of malignancy and the worst prognosis. Although standard therapeutic approaches, including surgical resection, radiotherapy, and chemotherapy, are routinely applied, the prognosis of glioma, especially GBM, remains poor. Metabolic rewiring is widely recognized as a major characteristic of malignant tumors and is especially evident in glioma. Recent studies have shown that fatty acid metabolic rewiring is a widespread feature of glioma and plays an important role in its pathogenesis and therapeutic resistance. Therefore, targeting metabolic reprogramming, particularly aberrant fatty acid metabolism, may have potential therapeutic implications in glioma. This review systematically synthesizes the molecular mechanisms underlying abnormal fatty acid metabolism in glioma pathogenesis and treatment responses. It also elucidates the regulatory networks governing key fatty acid metabolic pathways and integrates emerging strategies targeting these pathways to enhance the therapeutic sensitivity of glioma cells. Ultimately, this review aims to provide a conceptual framework and future research directions for overcoming the current limitations of glioma treatment through metabolic therapy.</p>