Post-harvest losses and food waste have become critical challenges in the global food supply chain, contributing to economic losses, environmental degradation, and food insecurity. This article explores the innovative applications of post-harvest biotechnology and genetic engineering as promising solutions to address these issues by extending the shelf life of perishable products and minimizing food waste. Advancements in genetic engineering techniques have paved the way for the development of crops with enhanced resistance to pests, diseases, and environmental stresses. Additionally, the manipulation of genes associated with ripening and senescence has allowed scientists to engineer fruits and vegetables with extended shelf life. These genetically modified organisms (GMOs) exhibit improved post-harvest characteristics, providing a longer window for transportation, storage, and consumption. Biotechnological interventions also include the use of biocontrol agents and beneficial microorganisms to suppress post-harvest pathogens, thereby reducing spoilage and decay. The development of bio-preservatives, such as antimicrobial peptides and natural compounds, offers an eco-friendly alternative to traditional chemical preservatives, contributing to both food safety and sustainability. Furthermore, the integration of smart packaging technologies with genetic modifications enhances the monitoring and control of environmental conditions during storage and transportation. Intelligent packaging materials equipped with sensors can detect changes in temperature, humidity, and gas composition, enabling real-time adjustments to prolong the freshness of perishable goods.