To investigate the interaction and elusive underlying mechanism of soil drought and vapour pressure deficit (VPD) on plant growth and water use efficiency (WUE), tomato plants (Solanum lycopersicum) (wild type and its ABA-deficient mutant) were grown under two different VPD environments. The parameters like stomatal conductance (gs), plant water relations, WUE, abscisic acid concentration (ABA) in leaf and xylem sap, carbon and oxygen isotope composition in leaf (δ13Cleaf and δ18Oleaf) were measured to estimate the physiological basis of VPD and drought in these genotypes of tomato. The results showed that, in relation to relatively higher VPD (ca. 1.15 kPa), lower VPD (ca. 0.55 kPa) significantly improved plant water status including leaf relative water content, leaf water potential and root water potential. Lower VPD chamber increased dry mass increment but decreased daily transpiration and plant water use, hereby improving WUE. Under drought conditions, decrease in plant water status and gs occurred in the wild type plants, along with higher concentration of ABA in leaf and xylem sap. However, there was no significant difference in plant WUE between the soil-droughted plants and the well-watered controls. And the interaction of soil drought and VPD on WUE was not significant. In contrast, plant WUE was superior in the wild type plants, especially under lower VPD environment. These findings help to understand the mechanism of stomata response to drought under varied environments of VPD. It could provide useful information for tomato cultivation under climate-controlled environments.