Grafting is considered to be a unique component in sustainable vegetable production. In addition to its usefulness for managing soil-borne diseases, it has been suggested that grafting with vigorous rootstocks can improve crop growth and yield. The objective of this greenhouse study was to assess the effects of different interspecific hybrid tomato rootstocks (Solanum lycopersicum × Solanum habrochaites) on yield, growth, nutrient accumulation, and fruit composition of tomato (S. lycopersicum). Using the determinate tomato cultivar Florida 47 as the scion, plants were grafted onto four interspecific rootstock cultivars including Beaufort, Maxifort, Multifort, and RST-04-105. Overall, the use of rootstocks resulted in total and marketable fruit increase 53% and 66% higher than non-grafted and self-grafted scion plants, respectively. The increase in marketable yield by ‘Beaufort’, ‘Maxifort’, and ‘Multifort’ was largely attributed to an increased number of fruit per plant, whereas higher average fruit weight contributed to the yield increase in plants grafted onto ‘RST-04-105’. Self-grafting of ‘Florida 47’ resulted in similar yield as the non-grafted scion control. Analyses of plant growth parameters demonstrated significant enhancement of total leaf area at first fruit harvest in plants grafted onto interspecific rootstocks as compared with the non-grafted and self-grafted scion controls. In addition to plant growth and yield improvement, enhanced accumulation of nitrogen, potassium, and calcium was also observed in grafted plants. The enhancement in mineral nutrient accumulation was largely related to increased biomass accumulation rather than higher nutrient concentration (on a dry weight basis). The overall accumulation of phosphorus was not influenced markedly by the rootstocks used. In general, grafting with the interspecific rootstocks maintained fruit soluble solids content (SSC) and total titratable acidity (TTA), concentrations of vitamin C, carotenoids, and total phenolics at levels comparable with non-grafted plants, whereas harvest date showed a more pronounced effect on fruit composition.