Shahrukh Khan, ZEENAT KORAI, Liting Yang, Shakal Khan Korai, Shengnan Li, Usman Zulfiqar, Mohammed S. Alotaibi, Dilnozakhon Asadullaeva, Muydinjon Muminov, Mayank Anand Gururani, X Wang
Plants adapt to biotic and abiotic stresses through extensive metabolic reprogramming that reallocates cellular resources toward defense while maintaining metabolic homeostasis. This process is tightly regulated by interconnected signaling networks, in which phytohormones, including salicylic acid, jasmonic acid, ethylene, and abscisic acid, integrate stress perception with transcriptional and metabolic responses. Recent advances in metabolomics have enabled systems-level characterization of these dynamic processes, revealing how metabolic pathways are coordinately rewired during stress adaptation. In this review, we synthesize current understanding of the mechanistic links between early signaling events and downstream metabolic outcomes. We highlight how stress perception through pattern recognition receptors, Ca2+ influx, reactive oxygen species, and mitogen-activated protein kinase cascades is coupled to transcriptional and post-transcriptional regulation of both primary and specialized metabolisms. Key metabolic adjustments include reconfiguration of central carbon metabolism, maintenance of redox balance, and induction of defense-associated compounds such as phenylpropanoids, flavonoids, terpenoids, and phytoalexins. We further examine the metabolic basis of the growth-defense trade-off, emphasizing the roles of TARGET OF RAPAMYCIN (TOR) and SNF1-RELATED KINASE 1 (SnRK1) in coordinating energy allocation under stress conditions. Emerging approaches, including targeted and untargeted metabolomics, spatial and temporal profiling, stable isotope-assisted fluxomics, and multi-omics integration, are discussed as key tools for dissecting plant defense metabolism. Despite these advances, challenges remain in linking metabolic changes to causal defense functions and in resolving context-dependent responses under complex stress conditions. Collectively, this review provides a mechanistic and systems-level framework that connects signaling networks with metabolic reprogramming, offering new opportunities for improving crop resilience through metabolic engineering and precision breeding.