Powerfuels produced with renewable electricity are considered a promising option for greenhouse gas mitigation in various sectors. Global scenarios indicate an accelerated and substantially increasing demand for powerfuels to achieve international climate targets. Consequently, a new industrial sector is expected to emerge in the coming decades with links into several transport and manufacturing industries. Past experiences, such as with biofuels, have demonstrated the importance of adopting a holistic perspective when dealing with the implications of a new sector to avoid adverse effects on both people and the planet. Therefore, the objective of this chapter is to define a framework that encompasses the opportunities and risks associated with powerfuels for people, the planet, and prosperity—the three main areas of action next to “peace” and “partnerships” that the United Nations Sustainable Development Goals are categorized against. This framework not only identifies minimum criteria for powerfuels but also considers potential socioeconomic co-benefits at global, regional, and local levels. The approach derives the impacts based on the concept of planetary boundaries and globally shared values, as manifested in international agreements on climate, prosperity, and human rights. The findings of this work reveal that existing sustainability definitions for powerfuels, as exemplified at the European level, seem insufficient to avoid negative impacts. Consequently, there is a need to further advance the sustainability discourse, particularly at the political level.