Drought stress and nutrient deficiency are limiting factors in vegetable production that will have a decisive role due to the challenges of climate change in the future. The negative effects of these stressors on yield can be mitigated by crop grafting. The increasing demands for resource-use efficiency in crop production, therefore, require the development and phenotyping of more resilient rootstocks, and the selection of appropriate scions. We tested the effect of combined drought stress and nutrient deficiency on yield and fruit quality of the two tomato cultivars ‘Lyterno’ and ‘Tastery’ in the greenhouse, grafted onto different rootstock genotypes. The use of four different rootstocks, including two novel S. pennellii × S. lycopersicum hybrids and the proven-effective use of ‘Beaufort’, as well as self-grafted plants, allowed conclusions to be drawn about the differential stress mitigation of the rootstocks used. The stress-induced yield reduction of the scion ‘Lyterno’ can be mitigated more significantly by the novel hybrid rootstocks than by the commercial rootstock ‘Beaufort’. At the same time, however, the individual fruit weight and the lycopene content of the fruits were significantly reduced when grafted onto the hybrid rootstocks. In contrast, the cultivar ‘Tastery’ showed a weak stress response, so that a generally positive influence of the rootstocks independently of the scions could not be demonstrated. We conclude that, particularly for more sensitive cultivars, the selection of more resilient rootstocks offers the potential for sustainable and resource-efficient production not competing with the overall quality of tomatoes.