Modeling as a tool solves extremely difficult tasks in life sciences. Recently, schemes of culturing of microalgae have received special attention because of its unique features and possible uses in many industrial applications for renewable energy production and high value products isolation. The goal of this review is to present the use of system analysis theory applied to microalgae culturing modeling and process development. The review mainly focuses on the modeling of the key steps of autotrophic growth under the integral biorefinery concept of the microalgae biomass. The system approach follows systematically a procedure showing the difficulties by modeling of sub-systems. The development of microalgae kinetics and computational fluid dynamics (CFD) studies were analyzed in details as sub-systems in advanced design of photobioreactor (PBR). This review logically follows the trends of the modeling procedure and clarifies how this approach may save time and money during the research efforts. The result of this work is a successful development of a complex PBR mathematical analysis in the frame of the integral biorefinery concept.