As a result of the climate changes that are getting worse nowadays, drought stress (DS) is a major obstacle during crop life stages, which ultimately reduces tomato crop yields. So, there is a need to adopt modern approaches like a novel nutrient- and antioxidant-based formulation (NABF) for boosting tomato crop productivity. NABF consists of antioxidants (i.e., citric acid, salicylic acid, ascorbic acid, glutathione, and EDTA) and nutrients making it a fruitful growth stimulator against environmental stressors. As a first report, this study was scheduled to investigate the foliar application of NABF on growth and production traits, physio-biochemical attributes, water use efficiency (WUE), and nutritional, hormonal, and antioxidative status of tomato plants cultivated under full watering (100% of ETc) and DS (80 or 60% of ETc). Stressed tomato plants treated with NABF had higher DS tolerance through improved traits of photosynthetic efficiency, leaf integrity, various nutrients (i.e., copper, zinc, manganese, calcium, potassium, phosphorus, and nitrogen), and hormonal contents. These positives were a result of lower levels of oxidative stress biomarkers as a result of enhanced osmoprotectants (soluble sugars, proline, and soluble protein), and non-enzymatic and enzymatic antioxidant activities. Growth, yield, and fruit quality traits, as well as WUE, were improved. Full watering with application of 2.5 g NABF L−1 collected 121 t tomato fruits per hectare as the best treatment. Under moderate DS (80% of ETc), NABF application increased fruit yield by 10.3%, while, under severe DS (40% of ETc), the same fruit yield was obtained compared to full irrigation without NABF. Therefore, the application of 60% ETc × NABF was explored to not only give a similar yield with higher quality compared to 100% ETc without NABF as well as increase WUE.