The inclusion of exogenous phytase in P- and Ca-deficient diets of broilers to address the growing concern about excessive P excretion into the environment over the years has been remarkably documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with a meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to achieve the following: (1) quantitatively summarize the size of phytase effect on growth performance, bone strength and mineralization in broilers fed diets deficient in P and Ca and (2) estimate and explore the heterogeneity in the effect size of outcomes using subgroup and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration’s SYRCLE risk of bias checklists for animal studies. Applying the random effects models, Hedges’ g effect size of supplemented phytase was calculated using the R software (version 4.3.3, Angel Food Cake) to determine the standardized mean difference (SMD) at a 95% confidence interval. Subgroup analysis and meta-regression were used to further explore the effect size heterogeneity (PSMD ≤ 0.05, I2 > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and improves FCR at each time point of growth (p < 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (p < 0.0001) of broilers fed P- and Ca-deficient diets. The results of the subgroup and meta-regression analyses showed that the age and strain of broiler, dietary P source, and the duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary-available phosphorus and calcium and improve ADFI, BWG, and FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and the bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and the duration of phytase exposure rather than the dosage.