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• Metabolite and transcript profiles of melons grown at 7 US locations were analyzed. • Enrichment of esters in TTDV was detected. • Lipid-derivatives were enriched and carotenoids were depleted in honeydew cultivars. • Association analysis identified differential gene expression of transcripts linked to carotenoids and ester level QTLs in TTDV and honeydews. Melon (Cucumis melo) is an important crop grown worldwide. The diversity of aromatic volatiles melon fruits produce contributes to their diverse flavors. However, little is known about the chemical and molecular profiles essential for establishing the signature flavors in field conditions. Here we analyzed the metabolome and transcriptome of 10 melon varieties grown in the field in Weslaco, TX. Also, two cultivars (TTDV and F39) grown at seven locations in the US were studied further to understand how geographic conditions influence levels of metabolites and transcripts. The data obtained here were combined with sensory data, and the relationship between observed metabolites/transcripts and fruit quality QTL was evaluated. Overall, esters and lipid-derived metabolites varied significantly in different sample sets. TTDV variety was significantly enriched for esters, whereas honeydew varieties were for lipid-derived metabolites, separating their profiles from other varieties. Among transcripts associated with cultivar-specific metabolites, we identified several transcripts linked to QTLs responsible for the production of fruit metabolites, including benzyl alcohol O-benzoyltransferase (AAT2) and caffeic acid 3-O-methyltransferase 1-like. On the other hand, transcripts associated with location-specific metabolites did not produce a clear overlap with known fruit-quality QTLs, suggesting the presence of different regulatory systems for the environmental control of fruit metabolites. [ABSTRACT FROM AUTHOR]