Black soldier fly (Hermetia illucens) larvae meal have been used as feed protein supplements in fish feed, but few researches have investigated the metabolomic effects of Hermetia illucens larvae meal supplements. Therefore, the metabolic effects on Nile tilapia were investigated by replacing 5%, 10%, and 20% of the dietary soybean meal in the basal diet with Hermetia illucens larvae meal, respectively. This study shows that 20% H. illucens larvae meal feed could promote tilapia average daily gain of upto 5.03 ± 0.18 g (mean ± SEM). It was found that the tricarboxylic acid cycle efficiency was improved by activating the enzymes of mitochondrial isocitrate dehydrogenase, NAD-malate dehydrogenase, succinate dehydrogenase, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase, which then increased the output of ATP and NADH. Furthermore, amino acid and protein biosynthesis was boosted by enhanced glutamine synthetase and glutamate synthase. In particular, GSH increased with increased H. illucens larvae meal. Unsaturated fatty acid biosynthesis was stimulated by higher levels of fatty acid synthase and acetyl CoA carboxylase. Additionally, there was no significant change in lipase levels. Thus, the higher acetyl Co-A content was primarily involved in fatty acid biosynthesis and energy metabolism. Flavor substances, such as nonanal and 2-methyl-3-furanthiol, also accumulated with the addition of H. illucens larvae meal, which increased the umami taste and meat flavor. Additionally, the flavor of tilapia was improved owing to a decrease in trimethylamine content, which causes an earthy and fishy taste. This study uncovers a previously unknown metabolic effect of dietary H. illucens larvae meal on Nile tilapia.