We compared the efficacy of the Indian Farmers Fertilizer Cooperative (IFFCO) liquid nano urea formulation (NUF) and conventional urea on the model plant Arabidopsis thaliana. NUF and equimolar bulk urea were applied to vermiculite-grown one-month-old plants as 0.4% foliar sprays. NUF resulted in a 0.4 g increase in biomass, 0.5 mg g^{− 1} in chlorophyll, 0.17 mmol g^{− 1} in nitrogen, and 28.8 mg g^{− 1} in amino acid content of the leaves, compared to bulk urea. NUF’s zeta potential of -54.7 mV and particle size of ≃27.7 nm, measured by dynamic light scattering and transmission electron microscopy, is suitable for stomatal uptake. A differential gene expression analysis of NUF versus urea-treated plants showed significantly higher expression levels of 211 genes (log₂fold-change > 0.5, FDR < 0.05) involved in the biosynthesis of carbohydrates, amino acids, nucleotides, lipids, phytohormones, and secondary metabolites, cell wall biosynthesis and modification, growth and developmental processes, cell cycle, and stress response than bulk urea. On the other hand, 1,286 genes (log₂fold-change < -0.5) involved in cell death, abscission, senescence, nitrogen transport and metabolism, and biotic stress response showed lower expression levels upon NUF application than bulk urea. These suggest that although NUF suppresses nitrogen uptake genes, it enhances growth by higher induction of essential biomolecule synthesis and growth-promoting genes, than bulk urea. This research advances current knowledge in sustainable agriculture by elucidating the molecular mechanisms through which nano urea enhances plant productivity compared to bulk urea, potentially reducing fertilizer use.