Nowadays, eco‐designing products is increasingly practiced. The next challenge for sustainability is to optimize production processes. Biorefineries are particularly concerned with this improvement, because they use renewable resources. To identify the contribution of transformation processes to the overall environmental impacts, Life Cycle Assessment (LCA) appears as the adequate method. A literature review highlights that LCA is mainly performed on biorefineries to compare biomass feedstocks between them and to a fossil reference. Another part of environmental LCA compares the impacts of different processing routes. Nevertheless, these evaluations concern already designed processes. Generally, processes are considered as a unique operation in assessments. However, some criteria like operating can notably modify environmental burdens. The eco‐design of biorefinery processes can be guided by coupling process simulation to LCA. This method has been emerging in the chemical sector in recent years. Consequently, this paper proposes a new methodological approach to assessing the complete sustainability of biorefinery processes, since its first design stages. In addition to coupling process simulation and environmental LCA, the other pillars of sustainability will be assessed. Indeed, Life Cycle Costing and Social Life Cycle Assessment can be performed to obtain an integrated methodological framework. The simultaneous optimization of the environmental, economic, and social performances of the process can lead to antagonist ways of improving. Consequently, compromises should be realized. Thereby, the multi‐objective optimization can be accomplished by a metaheuristic method supported by a decision‐making tool. Finally, the main limits of this method and some perspectives and ways for improving are discussed. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd