Food security and crop production are challenged worldwide due to overpopulation, changing environmental conditions, crop establishment failure, and various kinds of post-harvest losses. The demand for high-quality foods with improved nutritional quality is also growing day by day. Therefore, production of high-quality produce and reducing post-harvest losses of produce, particularly of perishable fruits and vegetables, are vital. For many decades, attempts have been made to improve the post-harvest quality traits of horticultural crops. Recently, modern genetic tools such as genome editing emerged as a new approach to manage and overcome post-harvest effectively and efficiently. The different genome editing tools including ZFNs, TALENs, and CRISPR/Cas9 system effectively introduce mutations (In Dels) in many horticultural crops to address and resolve the issues associated with post-harvest storage quality. Henceforth, we provide a broad review of genome editing applications in horticulture crops to improve post-harvest stability traits such as shelf life, texture, and resistance to pathogens without compromising nutritional value. Moreover, major roadblocks, challenges, and their possible solutions for employing genome editing tools are also discussed.