Despite the fact that there are wastewater treatment plants (WWTPs) currently operational across Iran and great advances have been made in this area, there are still problems in the design, construction, and operation of WWTPs with large nonlinear systems, varying flow rates, and pollution charges. The objective of this study was to investigate the effect of operating parameters including the return activated sludge (RAS) ratio, internal recycle (IR) ratio and dissolved oxygen (DO) concentration in an activated sludge system for the Modules 5&6 of the Southern Tehran WWTP. This study designed and simulated a plant based on the activated sludge model No.1 (ASM1) to determine the factors affecting wastewater treatment systems; then, the kinetic parameters were measured. The kinetic parameters such as the yield coefficient (Y), decay coefficient (Kd), maximum specific growth rate (K), and saturation constant (Ks) were in the range of 0.303-0.331g/g, 0.030-0.033d-1, 1.65-1.93d-1 and 37.6-44.92mg/l, respectively. The RAS ratios, IR ratios, and DO concentration varied from 0.2 to 2, 1 to 3.5, and 0.27 to 3.54 mg/l, respectively. The amount of RAS had the greatest impact on the effluent. The amounts of IR and DO concentration had no significant effect on the concentration of the five-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD), and total suspended solids (TSS) in the effluent. After the RAS, the amount of IR had the most direct effect on reducing the effluent total nitrogen (TN) concentration. As a result, the overall removal efficiency increased up to 75% when the IR rate was 200% of the influent flow rate, the RAS rate was 90% of the influent flow rate, and the DO concentration in the first aeration unit was 2 mg/l considering the aeration cost. Therefore, proper operating parameters can provide the best quality of effluent that meets environmental standards.