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Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Increased fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy. display that invasion. suggest a positive correlation between tumor cells’ slow proliferation rate, ZEB1 expression, invasion, and chemoresistance. Complementing those our results demonstrate increased mitochondria and OxPhos activities in the GBM SCC population. Interestingly, our bioinformatics analyses reveal an increased expression of genes regulating mitochondrial OxPhos in recurrent GBMs compared to primary tumors, and we have found an increased expression of mitochondria-specific genes in SCCs that are similar to those found in recurrent tumors. Chemoresistance has also show increased SCC survival and preferential utilization of lipids droplets in response to glucose restriction or glycolysis inhibition. Moreover, the metabolic resistance of SCCs to glucose deprivation or glycolysis inhibition can be prevented by the pharmacological inhibition or genomic deletion using CRISPR/Cas9 of FABP7, both of which block the uptake of fatty acids upstream of intracellular lipid metabolic pathways, in vitro and in vivo . Importantly, we have found that FABP7 inhibition leads to overall increased survival, whether alone or in combination with glycolysis inhibition, suggesting that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy. At high glucose concentrations, FABP7 inhibition did not prevent cell survival and proliferation, which suggests that the fatty acids can be synthesized for metabolism and energy production from other nutrients, including glucose or glutamine. We also found, in SCCs compared to FCCs, a significantly increased presence of autophagosomes and lysosomes and expression of associated pathways, which are known to mediate catabolic pathways that provide energy to cells in response to decreased nutrient availabilities. Future studies will be needed to determine whether lipid reserve utilization is dependent on those autophagosomal and lysosomal pathways. to compare the function The effects of FABP7 inhibition, alone or in combination with pharmacological