The United Nations has set a goal of eradicating hunger by the year 2030 in its sustainability goals; yet, achieving global food security seems to be a foolhardy goal. The root cause is not only a decline in crop production but also the loss at many stages of food handling, transportation, and storage, commonly termed post-harvest loss. The major food spoilage is primarily due to temperature variations, changes in humidity, and infestation by pests resulting in the perishing of the food. This spoilage reduces the quality, nutritional value, and shelf life of food, resulting in economic loss. Although conventional food packaging is used to avoid spoilage, it is not successful in combating post-harvest loss. Nanotechnology is a potentially useful approach to mitigate these issues, providing sustainable and environmentally friendly agricultural practices. This chapter explores the use of various nanomaterials (NMs) as nanocarriers, nanoemulsions, and nanoencapsulation to enhance the harvest yield and prevent post-harvest loss. Active and smart food packaging with the integration of NMs having antioxidant, antibacterial, and/or barrier protection potential increases the shelf life of the enclosed products. The chapter also highlights the associated challenges and future prospects of the application of nanotechnology in handling post-harvest loss.