BACKGROUND: Melatonin improves the production performance of animal furs, particularly in promoting wool and cashmere growth. Although most studies of melatonin enhancing cashmere growth have focused primarily on gene and phenotype levels, its impact on metabolites has not received attention. To investigate the influence of melatonin on metabolites, genes, gene‒metabolite interactions, and associated signaling pathways in secondary hair follicles (SHFs), we performed multiomics analyses of skin and blood samples collected 30 days after sustained melatonin release. RESULTS: The results demonstrated that two melatonin interventions during SHF anagen in cashmere goats induce the early growth of SHFs, increase the active secondary follicle density (ASFD), and improve cashmere yield and quality. Transcriptomic analysis revealed 509 differentially expressed genes (DEGs), including key genes such as KRTs and KRTAPs, and genes associated with the WNT signaling pathway (LEF1, WNT3/4, and FZD3/5), suggesting their critical roles in melatonin-mediated SHF development. Metabolomic analysis revealed 842 metabolites in the skin samples and 1,162 in the blood samples. Among these, 177 differentially regulated metabolites (DRMs) in the skin were significantly enriched in pathways such as alpha-linolenic acid metabolism, glyoxylate and dicarboxylate metabolism, the citrate cycle (TCA cycle), and several amino acid metabolic pathways. Similarly, 122 DRMs in the blood were enriched in pathways related to protein digestion and absorption, central carbon metabolism in cancer, and aminoacyl-tRNA biosynthesis. Finally, the integrative analysis revealed partially coenriched metabolic pathways and relationships between DEGs and DRMs. CONCLUSIONS: In summary, by integrating transcriptomics and metabolomics, this study provides novel insights into the role of melatonin in promoting SHF development. Furthermore, these findings establish a theoretical foundation for the broader application of melatonin-based technologies to promote cashmere growth.