The joint analysis of economic, environmental, and social aspects of biorefineries has been boosted in recent years. The sustainability assessment of biorefineries is considered a fundamental approach to determine the possible implementation of processes due to the inclusion of different stakeholders in the analysis. Few studies related to the sustainability of biorefineries have been reported due to the difficulty of including social aspects. Most of the studies related to the sustainability assessment of biorefineries do not report a sustainability framework. This fact decreases the comparison and reproducibility of the reported results. This paper gives some perspectives related to the sustainability assessment of biorefineries based on a short literature review. A methodological approach to define the sustainability framework to assess the three dimensions of sustainability is given as a tool to evaluate biomass upgrading processes and biorefineries. This proposed approach was applied to a case of study to valorize rejected unripe plantains in the Montes de Maria region, Colombia. The results show the sustainability of the sequential production of plantain flour and bioethanol using the whole unripe plantain (pulp + peel). A payback period of 3.5 y and the possibility to create more than 50 employees boost this process as a potential entrepreneurship alternative to be studied in a detailed way. However, the only production of plantain flour is recommended to decrease the environmental impact caused by the ethanol production process.