One of the main challenges for the 21st century is ensuring global food security. Today, maize is the largest staple crop produced worldwide. Postharvest primary insect pests, especially the maize weevil (Sitophilus zeamais) and the large grain borer (Prostephanus truncatus) cause food-grain losses during storage up to 40% of total production, mainly in developing countries. Alternatives for pest management have been explored, including the implementation of hermetic storage structures and the application of chemical insecticides. Nevertheless, in low-income regions, both strategies are rarely accessible to smallholders. Modern breeding programs have endeavored to develop insect-resistant varieties, which diminish postharvest pest losses. In this review, we report the current status and advances in maize kernel-pest interactions, the bases and mechanisms of kernel resistance and their biotechnological perspectives. We demonstrate that the comprehension of resistance mechanisms has been fundamental for the development of new productive and resistant varieties, representing a sustainable alternative for developing countries. Finally, we analyse the biotechnological perspectives of natural kernel resistance in global food security.