AIM: The present study aimed to elucidate which pathways contribute to cardiometabolic adaptation in Egyptian fruit bats. METHODS: Utilising cardiac tissues from Egyptian fruit bats (Rousettus aegyptiacus) and C57BL/6J mice, we combined liquid chromatography-mass spectrometry metabolic profiling, non-targeted ¹H NMR spectroscopy, and in silico computational modelling using the genome-scale mammalian network CardioNet. By integrating complementary untargeted and targeted metabolomics with genome-scale flux balance analysis, this approach enables systems-level inference of pathway activity beyond static metabolite abundance measurements. MAIN FINDINGS: Our analyses revealed that bat hearts exhibit a distinct metabolic profile characterised by depleted glycogen reserves and increased reliance on lipid oxidation to meet energy demands. Notably, bat hearts displayed elevated fluxes in oxidative phosphorylation, β-oxidation of long-chain fatty acids, and the Krebs cycle, alongside reduced amino acid catabolism. These findings suggest that bats have evolved unique metabolic strategies to support the high-energy demands of flight, maintaining cardiac function without succumbing to pathological remodelling. CONCLUSIONS: This study provides the first comprehensive insight into the metabolic adaptations in the cardiac tissue of a bat species, contributing to our understanding of how these mammals endure extreme physiological stresses.