Identifying optimal photobioreactor configurations and process operating conditions is critical to industrialize microalgae-derived biorenewables. Traditionally, this was addressed by testing numerous design scenarios from integrated physical models coupling computational fluid dynamics and kinetic modeling. However, this approach presents computational intractability and numerical instabilities when simulating large-scale systems, causing time-intensive computing efforts and infeasibility in mathematical optimization. Therefore, we propose an innovative data-driven surrogate modeling framework, which considerably reduces computing time from months to days by exploiting state-of-the-art deep learning technology. The framework built upon a few simulated results from the physical model to learn the sophisticated hydrodynamic and biochemical kinetic mechanisms; then adopts a hybrid stochastic optimization algorithm to explore untested processes and find optimal solutions. Through verification, this framework was demonstrated to have comparable accuracy to the physical model. Moreover, multi-objective optimization was incorporated to generate a Pareto-frontier for decision-making, advancing its applications in complex biosystems modeling and optimization. (c) 2018 American Institute of Chemical Engineers AIChE J, 65: 915-923, 2019