The nutritional composition of diets and the provision of exogenous phytases play important roles in animal performance. Therefore, we evaluated the individual and combined impact of metabolizable energy (ME), digestible lysine (dLys), available phosphorus (avP) and calcium (Ca), and phytase dose (1,000 or 2,000 FTU/kg) on the growth performance, feed efficiency, phosphorus digestibility, and bone ash content of broiler chickens from 10 to 42 d of age. Experimental diets were formulated in a Box-Behnken design to contain various levels of ME (11.9, 12.2, 12.54, or 13.1MJ/kg), dLys (0.91, 0.93, 0.96, or 1.00%) and avP/Ca (0.12/0.47, 0.21/0.58, or 0.33/0.68%). The effect of phytase was expressed in terms of the extra nutrients released. The diets were formulated to have consistent phytate substrate contents (0.28% in average). Body weight gain (BWG) and feed conversion ratio (FCR) were described via polynomial equations (R2=0.88 and 0.52, respectively), with interconnections between variables (ME, dLys, and avP/Ca). No interaction was observed among variables (P > 0.05). Metabolizable energy was the most important factor affecting BWG and FCR (linearly; P < 0.001). Reducing ME content from 13.1 to 11.9 MJ/kg in control diet resulted in a 6.8% decrease in BWG and a 3.1% increase in FCR (P < 0.001). The dLys contents also affected performance linearly (P < 0.001), but to a lesser degree; BWG decreased by 160g when the dLys was reduced by 0.09% units, while the same reduction in dLys increased the FCR by 0.108 points. The inclusion of phytase alleviated the negative effects on feed intake (FI), BWG, and FCR. Phytase improved phosphorus digestibility and bone ash content according to a quadratic relationship. When phytase was added, ME negatively affected FI (r=-0.82,P<0.001), whereas the dLys content was correlated with FCR (r=-0.80,P<0.001). Supplementing phytase allowed the reduction of ME, dLys, and avP-Ca in the diet without affecting performance. The addition of phytase increased of ME, dLys, and avP by 0.20 MJ/kg, 0.04 and 0.18% units for 1,000 FTU/kg and 0.4 MJ/kg, 0.06 and 0.20% units for 2,000 FTU/kg.