A method for designing the operating parameters (surface light intensity, operating temperature and agitation rate) was proposed for microalgal protein production. Furthermore, quadratic model was established and validated (R-2 > 0.90) with experimental data. It was recorded that temperature and agitation rate were slightly interdependent. The microalgal protein performance could be estimated using the simulated experimental setup and procedure developed in this study. The results also showed a holistic approach for opening a new avenue on simulation design for microalgal protein optimization.