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The wild Atractylodes lancea rhizomes have been traditionally used as herbal medicine. As the increasingly exhaustion of wild A. lancea, the artificial cultivation mainly contributed to the medicinal material production. However, besides the phenotypic variation of rhizome phenotypic trait alteration, the qualities of cultivated A. lancea decrease compared with the wild counterpart. To unveil the physiological and molecular mechanism beneath the phenotypic variation, GC-MS-based volatile organic compounds (VOCs) profiling and RNAseq-based transcriptome analysis were conducted. The volatile metabolomics profiling revealed 65 differentially accumulated metabolites (DAMs) while the transcriptomic profiling identified 12 009 differentially expressed unigenes (DEGs) post-cultivation. The volatile active compounds including atractylone, and eudesmol accumulated more in wild rhizome than in the cultivated counterpart, and several unigenes in terpene synthesis were downregulated under cultivated condition. Compared with the wild A. lancea rhizome, the contents of bioactive Jasmonic Acid (JAs) in cultivated A. lancea rhizome were higher, and evidences that JAs negatively regulate the terpenes biosynthesis in the cultivated A. lancea rhizome were also provided. The combinational omics analysis further indicated the high correlation between the ten cultivation-suppressed VOCs and the cultivation-altered genes for sesquiterpenoids biosynthesis in A. lancea. The network of the cultivation-altered transcription factors (TFs) and the ten VOCs suggested TFs (e.g. Arabidopsis ERF13 homologs and WRKY50) are involved in the regulation of terpenes biosynthesis. These results laid a theoretical basis for developing geo-herbalism medicinal plants with "high quality and optimal shape"., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)