Food systems are composed of interrelated activities that transform agricultural products into food. Their operations need to meet several food security, food safety, and sustainability requirements. Therefore, risk assessment of food systems must be multidisciplinary and include food safety, nutrition, environmental, economics, and social criteria. However, combining these criteria to assess multiple impacts remains a challenge in complex and multi-stakeholder systems. Until now, only a few holistic assessments, whether domain-oriented or generic and with different levels of quantification, have covered all criteria and the whole food systems. We reviewed and presented the various assessment methods and their applications in food systems, highlighting their advantages and disadvantages. Recommendations were made for a tiered approach combining different holistic assessment methods.