Foodborne illnesses result in a high disease burden worldwide, making food safety control of food business operations (FBOs) an urgent issue. With public agencies and FBOs facing challenges in monitoring the complex food supply chain with limited resources, scientific and objective insights into those factors that are related to food safety at FBOs are needed. These factors can be used as input for risk-based inspection. We conducted a systematic review to identify and analyze risk factors affecting the FBOs' food safety risk. We used a set of predefined search strings in Scopus and Web of Science to search for scientific manuscripts published in the English language between January 1 2003 and February 1 2023. The review identified 53 relevant studies and 43 risk factors. The presence of certified personnel turned out to be the most cited factor. Nearly half of the extracted factors had only been investigated in one study. Additional challenges were identified for developing a universal ready-to-use list of factors for the building of a risk-based inspection method, such as the limitation in the applicability of identified factors in different types of FBOs, and the variability in conclusions between publications for certain factors (e.g., FBO location and inspection history), stressing the need for additional research. Future studies should also prioritize standardizing definitions and measurements, particularly regarding compliance factors. In general, the current list of factors brought forward in our review lays the groundwork for building a transparent, objective, and risk-based method for food safety inspections of FBOs.