This study aimed to evaluate the effects of supplemental phytase with xylanase and β-glucanase blend on the apparent digestibility coefficient (ADC) of gross energy and nutrients, including amino acids, minerals, and nitrogen (N) and phosphorus (P) balance in Nile tilapia, Oreochromis niloticus. Diets were elaborated either without enzyme supplementation (control) or supplemented with phytase (PHY), xylanase and β-glucanase (XB) blend or a combination of phytase plus xylanase and β-glucanase (PHY+XB) blend. Fish (n = 192; 60 ± 3.4 g) were fed with the experimental diets replicated four times. Compared with the control group, fish-fed with the PHY+XB diet showed a higher ADC of gross energy and nutrients, including amino acids and minerals. Also, compared to control diet, digestible energy, digestible protein and available P contents were higher in fish-fed diet PHY+XB by 1.63 MJ kg−1, 7.21 and 4.70 g kg−1 diet respectively. Compared to the control group, fish-fed diet PHY+XB displayed lower total N and P loss of 17.51 and 10.09 g kg−1 of body weight gain (BWG) respectively. The study findings provided new insight into the nutritive value and ecofriendliness/sustainability of diets associated with exogenous enzymes for tilapia culture.