The practice of aquaculture is associated with the generation of a substantial quantity of effluent. Microalgae must effectively assimilate nitrogen and phosphorus from their surrounding environment for growth. This study modeled the algal biomass film, NO3–N concentration, and pH in the membrane bioreactor using the response surface methodology (RSM) and an artificial neural network (ANN). Furthermore, it was suggested that the optimal condition for each parameter be determined. The results of ANN modeling showed that ANN with a structure of 5-3 and employing the transfer functions tansig-logsig demonstrated the highest level of accuracy. This was evidenced by the obtained values of coefficient (R2) = 0.998, R = 0.999, mean squared error (MAE) = 0.0856, and mean square error (MSE) = 0.143. The ANN model, characterized by a 5-5 structure and employing the tansig-logsig transfer function, demonstrates superior accuracy when predicting the concentration of NO3–N and pH. This is evidenced by the high values of R2 (0.996), R (0.998), MAE (0.00162), and MSE (0.0262). The RSM was afterward employed to maximize the performance of algal film biomass, pH levels, and NO3–N concentrations. The optimal conditions for the algal biomass film were a concentration of 2.884 mg/L and a duration of 6.589 days. Similarly, the most favorable conditions for the NO3–N concentration and pH were 2.984 mg/L and 6.787 days, respectively. Therefore, this research uses non-dominated sorting genetic algorithm II (NSGA II) to find the optimal NO3–N concentration, algal biomass film, and pH for product or process quality. The region has the greatest alkaline pH and lowest NO3–N content.