A supply chain network MILP model, developed by means of AIMMS software, and a process plant simulation model, developed by means of Aspen Plus (R), are combined for the optimization of a biorefinery network. Optimization of the supply chain network is initially addressed using literature process and economic data. The results are used as input in the Aspen Plus (R) model where the technical and economic performance of the biorefineries is calculated rigorously. The two computational tools are iteratively executed until convergence on number, locations and size of the biorefineries and on process yield to products and total costs is achieved. The final results are used to perform the Economic Value and Environmental Impact (EVEI) analysis of the overall biorefinery network. The methodology is applied to a case study concerning the deployment of cereal straw in Germany to produce ethanol, ethyl levulinate and electricity. Optimization results reveal that the wheat straw supply network with four biorefineries is economically feasible and determines an environmental margin in terms of equivalent emissions savings of about 4 Mt of CO2 per year. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.