Cytokinins (CKs) are plant hormones controlling growth and development including cell division and differentiation, apical dominance and delay of senescence. CKs take part in regulation of the abiotic stress response in plants. In this study, transgenic tomato plants overexpressing the IPT (CK biosynthetic gene) were developed. Homozygous transgenic plants exhibited a phenotype with reduced plant stature and lost apical dominance. Increased shoot biomass and leaf water content with a reduction in fruit yield were observed in all transgenic lines. Proteomics analysis was conducted to understand high CK response in molecular level. Proteins supporting a strong sink phenotype and vasculature development were upregulated in transgenic lines and reflected the phenotypic changes observed in homozygous plants. Proteins related to stress response such as detoxification enzymes and PR proteins were upregulated in a gradual manner in transgenic lines with the strongest up-regulation in T6 homozygous line indicating the metabolic stress induced by high CK levels. The transgenic plants were tested for drought stress and observed to have improved water use efficiency, antioxidant response and delayed senescence compared to nontransgenic plants. Proteomic analyses from leaf total and nuclear enriched extracts were conducted to understand the molecular basis of improved drought tolerance. Proteins related to photosynthesis and oxidative stress response were the most prominent groups of differentially abundant proteins in the transgenic line under drought, which could contribute to tolerance. Eighteen transcription factors were differentially abundant in the nuclear proteome of drought stressed plants. These transcription factors could control the gene expression contributing to tolerance.