Nowadays, third-generation biorefineries have emerged as a viable method for capturing atmospheric CO2 and are known as a promising platform for various applications, including biofuels, high-value compounds for nutraceuticals, cosmetics, pharmaceuticals, animal and aquaculture feed, and biofuels. For large-scale microalgae production, the cultivation stage is crucial. The success of microalgae cultivation depends on the configuration and design of systems. Key factors include the direction and rate of aeration, light/dark cycle duration, light-time ratio, average turbulent kinetic energy, and other variables critical to microalgal growth. This chapter aims to provide fundamental knowledge on cultivation techniques, growth modes, cultivation conditions, requirements of photosynthetic microorganisms, and the modeling and control of photobioreactors. Additionally, it discusses future trends to enhance performance in microalgal biomass production for high-value compound production that can focus on the main problems encountered in microalgae cultivation and propose a new configuration in photobioreactors to perform and achieve maximum performance.