Acute kidney injury (AKI) caused by ischemia–reperfusion (I/R) remains a major cause of morbidity and mortality, often progressing to chronic kidney disease. No pharmacologic therapy effectively promotes tubular repair. Fibroblast growth factor 7 (FGF7), a paracrine ligand of FGFR2b, is known to drive epithelial regeneration. This study examined whether FGF7 signaling regulates metabolic and reparative responses in renal tubular cells following I/R injury. We combined human renal biopsy analysis, transcriptomic profiling in a murine I/R model, and both in vitro and in vivo validation. Expression of Fgf2, Fgf7, and Fgfr2 was measured across time points. Human proximal tubular (HK-2) cells were treated with recombinant human FGF7 (rhFGF7) to assess phosphorylation of ERK, AKT, and AMPK and expression of glycolytic enzymes-hexokinase 2 (HK2) and phosphofructokinase (PFK). Hypoxia was induced using cobalt chloride (CoCl₂) with or without FGFR2 inhibition. In mice subjected to renal I/R, rhFGF7 was administered to evaluate kidney function, ATP levels, metabolic enzymes, and fibrosis markers. In human renal cortex, FGF7 and FGFR2 were localized mainly to tubular epithelial cells with cytoplasmic and membranous staining. In AKI biopsies, FGF7 expression was markedly enhanced. In mice, transcriptomic analysis revealed a biphasic increase in Fgf7 and Fgfr2 after I/R, corresponding to early injury (day 7) and late repair (day 17) phases. In HK-2 cells, rhFGF7 rapidly activated ERK and AKT and suppressed AMPK phosphorylation, shifting energy metabolism from fatty acid oxidation to glycolysis. HK2 and PFK were upregulated in a dose-dependent manner, whereas fatty acid synthase decreased. Under CoCl₂-induced hypoxia, rhFGF7 reduced HO-1, NGAL, and caspase-3 expression; these effects were abolished by FGFR2 knockdown. In vivo, rhFGF7 treatment improved renal functional recovery, increased ATP content, restored HK2 and PFK expression, and decreased α-SMA levels, indicating metabolic restoration and reduced fibrosis. FGF7 is expressed in renal tubular epithelium and promotes recovery after I/R injury through activation of the FGF7–FGFR2–ERK/AKT axis and suppression of AMPK. This signaling reprograms metabolism from fatty acid oxidation to glycolysis, coupling energy restoration with tissue repair. FGF7 confers antioxidative and antifibrotic protection and represents a potential regenerative therapy for AKI and acute kidney disease.