The design and optimization of photobioreactor(s) (PBR) benefit from the development of robust and quantitatively accurate computational fluid dynamics (CFD) models, which incorporate the complex interplay of fundamental phenomena. In the present work, we propose a comprehensive computational model for tubular photobioreactors equipped with glass sponges. The simulation model requires a minimum of at least three submodels for hydrodynamics, light supply, and biomass kinetics, respectively. First, by modeling the hydrodynamics, the light–dark cycles can be detected and the mixing characteristics of the flow (besides the mass transport) can be analyzed. Second, the radiative transport model is deployed to predict the local light intensities according to the wavelength of the light and scattering characteristics of the culture. The third submodel implements the biomass growth kinetic by coupling the local light intensities to hydrodynamic information of the CO2 concentration, which allows to predict the algal growth. In combination, the novel mesoscopic simulation model is applied to a tubular PBR with transparent walls and an internal sponge structure. We showcase the coupled simulation results and validate specific submodel outcomes by comparing the experiments. The overall flow velocity, light distribution, and light intensities for individual algae trajectories are extracted and discussed. Conclusively, such insights into complex hydrodynamics and homogeneous illumination are very promising for CFD-based optimization of PBR.