N1-(2-chloro-4-pyridyl)-N3-phenylurea (CPPU), a synthetic cytokinin-active compound, is widely applied to induce parthenocarpic fruit set and enhance melon fruit enlargement (Cucumis melo L.). CPPU may also influence fruit quality; however, the mechanisms through which this occurs remain unknown. We investigated the differences in volatile emissions between parthenocarpic fruit set by CPPU (C) and seeded fruit set by artificial pollination (P). Gas chromatography–mass spectrometry (GC–MS) analysis revealed that six volatile organic compounds (VOCs) emitted by the P-group fruits were not detected in C-group fruits. The relative abundances of another 14 VOCs emitted by the CPPU-treated fruits were less than those in the P-group fruits. RNA sequencing analysis indicated that a total of 1027, 994, and 743 differentially expressed genes (DEGs) were detected in the C20 (treatment with 20 mg·L–1 CPPU) vs. P, P-C20 (pollination followed by 20 mg·L−1 CPPU treatment) vs. P, and P-C20 vs. C20 treatments, respectively. Compared with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the DEGs related to fatty acid degradation and metabolism, which contribute to volatile production, were enriched. In particular, DEGs such as carotenoid cleavage dioxygenase (CCD)-, lipoxygenase (LOX)-, alcohol dehydrogenase (ADH)-, and alcohol acyltransferase (ATT)-related genes were closely related to the formation of volatiles. In summary, our study provides a metabolic and transcriptomic atlas, reveals the impact of CPPU on VOCs, and enhances our understanding of the mechanisms of CPPU that contribute towards generally reducing the quality of melon fruit.