This study presents the development and implementation of a novel framework for optimal design of new and emerging renewable energy production systems by considering an iterative strategy which integrates the Net Present Value optimization along with detailed mechanistic modeling, simulation, and process optimization which yields optimal capacity plan, and operating conditions for the process. Due to the non-linear nature of process conversion mechanisms, metaheuristic algorithms are implemented in the framework to optimize operating conditions of process. Further, to apply complex kinetics in the process, we have made a linkage between process simulator (Aspen Plus) and Matlab. To demonstrate the effectiveness of the proposed methodology, a hypothetical case study of a lignocellulosic biorefinery is utilized. The proposed framework results reveal a deviation in optimal process yields and production capacities from initial literature estimates. These results indicate the importance of developing a multilayered framework to optimally design a renewable energy production system. (C) 2013 Elsevier Ltd. All rights reserved.