The current trial was designed to evaluate the positive impacts of different feed additives singly or in combination on the growth performance, nutritional parameters, intestinal histology, and gene expression of some growth and fat metabolism-related genes in the liver tissue of Nile tilapia. The experimented fish were allocated into eight groups in a glass aquarium (10 fish/aquarium in triplicate) with Pediococcus acidilactici, nanozeolites, and/or medium-chain fatty acid additives. The studied treatments were control (T0), nanozeolite (T1), Pediococcus (T2), medium-chain fatty acid (T3), nanozeolite + Pediococcus (T4), nanozeolite + medium-chain fatty acid (T5), Pediococcus + medium-chain fatty acid (T6), and nanozeolite + Pediococcus + medium-chain fatty acid (T7). The results of the growth and nutritional parameters (i.e., final body weight, total weight gain, feed intake, specific growth rate, feed conversion ratio, and protein efficiency ratio) of tilapia-fed diets supplemented with Pediococcus, nanozeolites, and medium-chain fatty acids improved, but the combination of these additives was significantly more effective. Moreover, expression of growth hormone receptor 1 gene was upregulated (P ≤ 0.05) in T7 fish when compared with T0, other groups showing intermediate values. Expression of insulin-like growth factor-1 was upregulated (P ≤ 0.05) in T5, T6, and T7 fish when compared with the other groups. The expression of the fatty acid-binding protein was higher in T6 and T7 fish (P ≤ 0.05) when compared with T0, T1, and T3 fish. In conclusion, combined additives had significant effects on improving growth and regulating growth-related genes.