The present study examined the impacts of two levels of selenium nanoparticles (SeNPs) on the Nile tilapia growth, survival, hematological and biochemical profiles, immunity, antioxidant activity, expression levels of growth-related genes, and histometric parameters of skeletal muscles. One hundred eighty monosex fingerlings (7.08± 0.08g) were randomly used to form three groups, with four replicates in each group. The first group was the control, which received a basal diet. The second group (treatment 1, T1) received 0.7mg/ kg diet SeNPs, while the third group (treatment 2, T2) was given 1.0mg/ kg diet SeNPs. The results indicated a growth enhancement in T2 (P< 0.05). In addition, a significant improvement in the feed conversion ratio was noticed in both T1 and T2 (P< 0.05). A longer mean survival time was demonstrated in T2 (P< 0.05). Significant improvements in the haematobiochemical parameters, immunological response, and antioxidant parameters in T2 fish were evident (P< 0.05). The expression of three growth-related genes, including growth hormone receptor, myostatin, and myogenin, were upregulated in T2. In contrast, the expression of myogenic factor 6 was downregulated in T2. Moreover, the histometric analysis revealed significantly larger muscle fibers in T2 than in the control and T1 (P< 0.05), indicating hypertrophy in T2. Additionally, the skeletal muscles from T1 had 19.38% more muscle fibers than T2 and 2.5% more muscle fibers than the control (P= 0.001). The current research not only indicated the positive impacts of SeNPs on the economic traits of the Nile tilapia but also investigated the underlying mechanisms responsible for these improvements on the cellular and molecular levels.