Facing the ecological and social crisis that the agrifood systems cross, a profound transformation of food systems is required, necessitating systemic and sustainable innovations. Sustainability assessments are generally performed to identify and/or validate the improvement in sustainability conferred by a designed artifact relative to the current or standard situation. However, they can have many other benefits in the design process. Here, we review the place, role, and conditions of use of sustainability assessment in innovation design processes in agrifood systems. By cross-referencing published findings and our own experience, we formalize a design process highlighting the place of sustainability assessment, whether design is intended for the creation of an agricultural or food artifact. We identify three types of assessment: initial diagnosis, screening between solutions at the ideation stage, and evaluation at the prototyping and development stages. We discuss ways of performing each of these assessments and highlight general key points about sustainability assessment. A first set of key points relate to criteria and indicators, a second set to the role of stakeholders, a third one to the adaptive nature of the assessment, and the last one to the uncertainty consideration. These key points provide guidance for efficient assessment in the design of innovations to increase the sustainability of agrifood systems. Thus, we demonstrate that the design process of innovations for sustainable agrifood systems requires (1) to formalize the place and mode of assessment, (2) to make use of relevant sustainability criteria and indicators, (3) to reinforce participatory practices, and (4) to adapt the assessment to the context of the designed artifact, to facilitate choices between imperfect solutions. Such an approach aims to promote innovations that meet the expectations of the system’s direct stakeholders, but also integrate the needs of invisible actors such as the environment or the well-being of populations.