In deammonification systems, nitrite-oxidizing bacteria (NOB) suppression and nitrous oxide (N2O) mitigation are two important operational objectives. To carry out this multivariable analysis of response, a comprehensive model for the N cycle was developed and evaluated against experimental data from a laboratory-scale deammonification granular sludge sequencing batch reactor. Different aeration strategies were tested, and the manipulated variables comprised the dissolved oxygen (DO) set point in the aerated phase, aeration on/off frequency (F), and the ratio (R) between the non-aerated and aerated phase durations. Experimental results showed that a high ammonium utilization rate (AUR) in relation to the low nitrate production rate (NPR) (NPR/AUR = 0.07-0.08) and limited N2O emissions (EN2O < 2%) could be achieved at the DO set point = 0.7 mg O2/L, R ratio = 2, and F frequency = 6-7 h-1. Under specific operational conditions (biomass concentration, NH4+-N loading rate, and temperature), simulation results confirmed the feasible aeration strategies for the trade-offs between the NOB suppression and N2O emission. The intermittent aeration regimes led to frequent shifts in the predominating N2O production pathways, that is, hydroxylamine (NH2OH) oxidation (aerated phase) versus autotrophic denitrification (non-aerated phase). The inclusion of the extracellular polymeric substance mechanism in the model explained the observed activity of heterotrophs, especially Anaerolineae, and granule formation.