This work investigates the design and modeling of fully integrated processes which utilize renewable feedstocks as raw materials by evaluating alternative technology options and possible process integrations to select the optimal configuration according to calculated process yields and economic profit criteria. The analysis is carried out by exploiting the advantages of process simulation and a novel hybrid optimization framework which includes a two layer optimization strategy composed of strategic and operational level decisions. Additionally, an integrated software platform is developed to incorporate experimentally-derived kinetics of complex biological reactions in process simulation. To demonstrate the effectiveness of the proposed approach, an advanced biofuel production facility which has alternative technology choices for each section of the plant is utilized. The results prove the efficiency of the proposed approach, and an optimal configuration for a lignocellulosic biorefinely is obtained. (C) 2014 Elsevier Ltd. All rights reserved.