Objectives: Cucumis melo L. var. aegyptiacus cv. Ismailawi plant is a member of family Cucurbitaceae. This study aimed to identify volatile components of the pulp of the fruit and also to evaluate its cytotoxic activity. Methods: Automated rapid headspace solid phase micro extraction (SPME) was applied for extraction of the volatile components combined with gas chromatography coupled to mass spectrometry GC/MS for  identification of the compounds responsible for the specific aroma of the fruits, MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) was used for the evaluation of the cytotoxic activity of both petroleum ether and defatted methanol extracts of the fruits' pulp against 3 different tumor cell lines; colon (Caco-2), hepatic (HepG2) and cervix (HeLa) carcinoma cells. Results: Twenty volatile components were identified in the pulp of the fruits which were dominated by esters as the major class of components, with hexyl acetate representing the major constituent (23.07%). Petroleum ether extract of the pulp displayed mild cytotoxic activity against HepG2 cell line with IC₅₀ of (31.6) µg/ml, all results were standardized against doxorubicinpositive control. Conclusion: This is the first report for the evaluation of the volatile constituents of Cucumis melo L. var. aegyptiacus cv. Ismailawi fruits which can serve as a base for its differentiation from other similar varieties in the same family.