With the application of Advanced Manufacturing Technologies (AMTs), food manufacturers can operate outside of traditional volume-variety diagonal positions without the predicted performance penalties. Although food manufacturers produce high-variety and high-volume products with low cost and high quality, it is unavoidable that their high-variety production processes experience a high changeover frequency. Changeovers are not only time-consuming but are also accompanied by production losses. While the literature has emphasized the technical and technological aspects of changeovers, e.g. the Single Minute Exchange of Dies (SMED), most of these studies focussed on flexibility, time, and product quality. As food manufacturers’ production is capital-intensive with low-profit margins, it is essential for them to improve changeover efficiency and reduce changeover losses. This paper thus aims to understand changeover activities, identify the key factors influencing food losses during changeovers and develop a mechanism for improving overall production efficiency. To that end, an in-depth case study is conducted with a major European food manufacturer. This study identified nine key factors influencing changeover losses and developed an improvement framework with three key themes (working methods, knowledge management, and organizational design).