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We conducted an integrative system biology of metabolome and transcriptome profile analyses during pomegranate (Punica granatum L.) seed germination and utilized a weighted gene co-expression network analysis (WGCNA) to describe the functionality and complexity of the physiological and morphogenetic processes as well as gene expression and metabolic differences during seed germination stages. In total, 489 metabolites were detected, including 40 differentially accumulated metabolites. The transcriptomic analysis showed the expression of 6984 genes changed significantly throughout the whole germination process. Using WGCNA, we identified modules related to the various seed germination stages and hub genes. In the initial imbibition stage (stage 1), the pivotal genes involved in RNA transduction and the glycolytic pathway were most active, while in the sprouting stage (stage 4), the pivotal genes were involved in multiple metabolic pathways. In terms of secondary metabolic pathways, we found flavonoid 4-reductase genes of anthocyanin biosynthesis pathway are most significantly affected during pomegranate seed germination, while the flavonol synthase gene was mainly involved in the regulation of isoflavonoid biosynthesis.