Annually, the world is losing 1.3 billion tons of food, costing approximately $1 trillion, while emitting 8% of greenhouse gases, and consumes 25% of all agricultural water. More than 45% of the produced food is lost before consumption in Egypt, representing a major obstacle for achieving food security and sustainable agricultural development. Addressing this issue requires identifying the main causes for food losses and interpreting the interrelationships between them. In this study, a multi-stage sampling strategy is adopted to investigate 610 stakeholders including farmers, intermediates, and agro-processors. Twenty-two determinants of food losses and waste (FLW) mitigation are identified and categorized into four categories. The interrelationships between these categories are interpreted by the structural equations modeling (SEM). The results revealed that insufficient infrastructure and shortage of government legalizations are the main determinants for reducing FLW, followed by secondary causes, inadequate marketing systems, improper handling practices, and technological and environmental determinants. The direct and indirect interactions are identified and estimated. This study suggests interventions for reducing the FLW including a participatory, holistic, integrated, and multidimensional strategy considering the entire supply chain. Hence, these results could help policymakers, agro-investors, and international funding donors to design more sustainable intervention strategies for reducing FLW in developing countries, considering cost-effectiveness and simplicity of generalizing to achieve the environmental preservation, sustainable food supply chain, and the sustainable use of the limited resources at the local and global levels.