The fatty acid profile of vegetable oil from seeds of egusi melon (Cucumeropsis mannii Naudin) and watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai) collected from a local market in Imo State, Nigeria, were analyzed using the GC-MS technique. The study revealed the presence of six (6) fatty acids in each seed oil. Four fatty acids and three fatty acid methyl esters were detected. A total of five (5) similar fatty acids (three (3) saturated and two (2) unsaturated) were detected in both oil, and both seed oils contained one fatty acid not detected in the other. The percentage (%) concentration of saturated fatty acids compounds detected in both oil include Pentadecanoic acid methyl ester (EMO: 4.91; WMO: 4.43), Octadecanoic acid (Stearic acid) (EMO: 3.64; WMO: 41.77), and Methyl heptacosanoate (EMO: 39.16; WMO: 1.32) while the (%) concentration of unsaturated fatty acids detected in both oils includes 11-octadecenoic acid, methyl ester, (EMO: 46.05; WMO:46.28) and Oleic acid (EMO: 4.48; WMO: 3.97). Eicosanoic acid, methyl ester was detected at a concentration of 1.77% in Egusi melon seed oil alone while watermelon seed oil detected n-Hexadecanoic acid at a concentration of 2.22%. The fatty acid profiling of both seed oil revealed fatty acid compounds with therapeutic abilities. This study has provided the scientific backing for the therapeutic uses of both oil and also has compared both oil and predicts a future substitution of both oil in future utilization and at the same time influence their acceptability by the consumers.