Grafting is a horticultural technique widely practiced in vegetable crops with the main objectives of providing protection against soil-borne diseases, enhancing tolerance against biotic and abiotic factors, increasing harvest time, and ultimately improving fruit quality and yield. Compatibility of scion and rootstock is the first and the most important step in grafting to be successful. Successful grafting requires various physiological metabolites and a complex network of molecular mechanisms that are active at the graft junction and play a vital role in revascularization at graft union after grafting. They are significantly linked with the development of scion, which in turn enhances fruit quality and improves tolerance against both biotic and abiotic constraints. Although conventional breeding techniques and biotechnological tools can be utilized to evolve tolerant cultivars but they require considerable time. As an alternative, grafting has the ability to improve the performance of high-yielding cultivars for enhanced adaptability to various biotic and abiotic stresses. Creation of robust and resilient rootstocks can further help to expand the use of vegetable grafting and advance socio-economic-environmental sustainability in agriculture and food security.