Vegetable crops are main sources for human nutrition because they have high nutritional value including vitamins, and minerals, as well as several bioactive compounds. Producing safe and healthy vegetables for human diet is of a great global issue, which needs to exploit all available arable lands for this production. This production should be achieved under stressful conditions including soil stress (mainly saline, alkaline-saline, waterlogged and low fertile soils), climatic stress (drought, flooding, saltwater intrusion, and heat stress), and along with normal conditions. Nano-biofortification can support the vegetable productivity especially by using the biological nano-nutrients. Bio-nanonutrients have many distinguished properties such as higher biological activity, lower toxicity, and better bioavailability than mineral forms. Bio-nanonutrients also can promote the vegetable growth, productivity and enhance their tolerance to different stresses by reinforcing the function of antioxidant enzymes. Thus, the producing biofortified vegetables under stressful conditions might be a sustainable solution particularly by using the biological nanonutrients like selenium. The controlling factors that are needed for a successful nano-biofortification program of vegetables are correlated with growing media, plant species, and method application of nanonutrients. The over dose of nanonutrients can cause a nanotoxicity for cultivated plants, and then human health after consumption. This problem can be managed by following the 4R Nutrient Stewardship concept, which focuses on the right rate, right source, right time, and right place.