Atmospheric CO2 concentration may rise up to 1000 ppm before the end of the century (IPCC, 2021). This will lead to profound changes in major physiological processes in plants (Gojon et al., 2022). On one hand, the stimulation of growth by the elevation of CO2 increases the production of plant biomass. On the other hand, elevated CO2 (eCO2) negatively affects plant nutrition and mineral composition, and alters water use efficiency and heat tolerance. Here, we report the results from transcriptomic, genetic and genomic approaches done to understand the effects of eCO2 on plant nutrition and responses to water deficit (WD) and elevated air temperature (HT), and to identify their genetic and molecular determinants. We notably demonstrated that eCO2 targets regulatory modules specifically associated with the regulation of high- affinity root nitrate transport, resulting in a decrease in the efficiency of root nitrate uptake. We also used natural genetic diversity to explore the phenotypic plasticity of A. thaliana under eCO2 and different combinations of WD and HT, and identified genotype-by-environment effects. Finally, we performed large-scale phenotyping of ionome content in A. thaliana natural populations under eCO2 followed by GWAS to analyze the genetic architecture of the response of A. thaliana to eCO2 and to identify genes involved in the adaptation to the current climate change.