Microalgae have been exploited for food, biofuels, animal feed and pharmaceutical products over the last few decades. The microalgae biotechnology has grown and diversified significantly, despite these developments the number of commercially available products are still limited and thus there is a significant need to increase the production. Modeling and optimization are used to simulate the behavior of the studied problems and provide a basis for selecting optimum input settings that optimize the outputs. This paper investigates the effect of the beijerinck solution (BS), phosphate solution (PS) and hunter trace (HT) with different four levels (values) on the biomass productivity (BP), lutein productivity (LP) and total chlorophyll (TC) in microalgae Chlorella pyrenoidosa. A closer look at the effect of each level of the input factors on the output factors is given. Various modeling techniques, such as the spline model and Gaussian Kriging model, are investigated to recommend the optimal models for describing the relationships between the input factors and each output factor. The validation and efficiency of the recommended models are studied from various points of view. Based on the recommended models, the predicted values of the BP, LP and TC are given for all the possible level-combinations (conditions) of the BS, PS and HT and the best (optimal) level-combinations of the BS, PS and HT that maximize the BP, LP and TC are recommended.