Studying the metabolic patterns underlying the key quality traits during the growth and development of melon is very important for the quality improvement and breeding of melon fruit. In this study, we employed transcriptomics and metabolomics to analyze the primary metabolic changes occurring in melon ('Xizhoumi 25') across five growth and development stages. We identified a total of 666 metabolites and their co-expressed genes, which were categorized into five different metabolic and gene modules. Through the analysis of these modules, the main metabolic pathways during the growth and development of melon were demonstrated from a global perspective. We also discussed the contribution of sucrose accumulation, the TCA cycle, and amino acid metabolism to the quality and flavor of melon. Enzymes related to amino acid metabolism were proposed, including Amine oxidase (AOC), aldehyde dehydrogenase (ALDH), tryptophan synthase (TRPB), etc. These results and data can provide new insights for further study on the metabolic regulation of melon quality and improve fruit quality.