A systematic design methodology is developed for producing two main products plus side products starting with one or more bio-based renewable source. A superstructure that includes all possible reaction and separation operations is generated through thermodynamic insights and available data. The number of alternative processes is systematically reduced through a screening procedure until only feasible alternatives are obtained. As part of the methodology, process intensification involving reactionseparation tasks is also considered to improve the design by shifting the equilibrium reactions. Economic analysis and net present value are determined to find the best economically and operationally feasible process. The application of the methodology is presented through a case study involving biodiesel and fatty alcohol productions.