Bioethanol is becoming increasingly attractive for the reasons of energy security, diversity, and sustainability. As a result, the use of bioethanol for transportation purposes has been encouraged extensively. However, designing an effective bioethanol supply chain that is both sustainable and robust is still questionable. Therefore, this research focuses on designing a bioethanol supply chain that is: 1) sustainable in improving economic, environmental, social, and energy efficiency aspects; and 2) robust to uncertainties such as bioethanol price, bioethanol demand and biomass yield. In this research, we first propose a decision framework to design an optimal bioenergy-based industrial symbiosis (BBIS) under certain constraints. In BBIS, traditionally separate plants collocate in order to efficiently utilize resources, reduce wastes and increase profits for the entire BBIS and each player in the BBIS. The decision framework combines linear programming models and large scale mixed integer linear programming model to determine: 1) best possible combination of plants to form the BBIS, and 2) the optimal multi-product network of various materials in the BBIS, such that the bioethanol production cost is reduced. Secondly, a sustainable hybrid generation bioethanol supply chain (HGBSC), which consists of 1st generation and 2nd generation bioethanol production, is designed to improve economic benefits under environmental and social restrictions. In this study, an optimal HGBSC is designed where the new 2nd generation bioethanol supply chain is integrated with the existing 1st generation bioethanol supply chain under uncertainties such as bioethanol price, bioethanol demand and biomass yield. A stochastic mixed integer linear programming (SMILP) model is developed to design the optimal configuration of HGBSC under different sustainability standards. Finally, a sustainable industrial symbiosis based hybrid generation bioethanol supply chain (ISHGBSC) is designed that incorporates various industrial symbiosis (IS) configurations into HGBSC to improve economic, environmental, social, and energy efficiency aspects of sustainability under bioethanol price, bioethanol demand and biomass yield uncertainties. A SMILP model is proposed to design the optimal ISHGBSC and Sampling Average Approximation algorithm is used as the solution technology. Case studies of North Dakota are used as an application. The results provide managerial insights about the benefits of BBIS configurations within HGBSC.