Increasing atmospheric CO2 concentration is one of the dominant factors to cause climate change by contributing to global warming. Heat and drought are important abiotic stresses reducing crop production and which often occur simultaneously. It will be more difficult to obtain the optimum grain yield from field-grown crops in future under the threat of increasing temperature and frequent spells of drought. Grown in over 85 countries, wheat (Triticum aestivum L.) is globally the third most produced staple crop behind rice and maize and thus, it is important for global food security. In this PhD project, a series of experiments were conducted with the overall objective to evaluate the potential of diverse wheat genotypes under drought conditions in the field and how elevated CO2 can modulate the negative effect of drought and heat when grown under controlled greenhouse conditions. Experiment-I was designed to assess the genetic diversity for yield-related traits in wheat grown under irrigated and terminal drought stress by next generation sequencing. To serve the objective, breeding lines derived from synthetic x elite cultivars and landraces x elite cultivars were evaluated under field conditions in Mexico. Terminal drought stress was implemented by stopping irrigation at and post anthesis. The germplasm was evaluated over two seasons. Genome wide association studies (GWAS) and haplotype-based mapping was utilized to track the genetic gain in terms of grain yield for terminal drought to find rare haplotypes responsible for drought tolerance. The haplotypes-based genome wide association study (GWAS) revealed significant associations with grain yield, spike length and thousand kernel weight, respectively, on three chromosomes. Likewise, significant associations were identified for the number of grains spike-1 and kernel abortion on the same chromosome. The genomic analysis information generated in the study can be efficiently utilized to improve yield and yield related parameters under terminal drought stress through marker-assisted breeding. In experiment II (A), responses of two contrasting wheat genotypes (L2 & L3) to drought stress was investigated under ambient and elevated CO2. CO2 elevation sensitized the responses to soil drying by reducing evapotranspiration in plants of both genotypes. Drought significantly affected the levels of different growth- and stress-related phytohormones, subsequently impacting physiological and yield-related traits. Elevated CO2 significantly increased the photosynthetic rate but not the yield-related traits. Genotype L3 accumulated more leaf tZ (CKs) and showed higher osmotic potential and spike SA/ABA ratio under combined drought and elevated CO2. L3 also had higher thousand kernel weight (TKW) and grain yield. It seems elevated CO2 is not necessarily increasing grain yield under drought conditions, and biophysiochemical characteristics may be valuable selection markers for obtaining higher TKW and grain yield in future drier and CO2-enriched environment. In experiment II (B), to improve our understanding of the physiological mechanism underlying grain yield reduction at anthesis drought, the responses of three spring wheat genotypes (L1, L2 and L3) having contrasting yield potential under drought in the field were investigated under controlled greenhouse conditions. Drought stress was imposed at anthesis stage by withholding irrigation until all plant available water was depleted. Specific carbohydrate-metabolic and antioxidant enzyme activities were correlating with yield-related traits i.e. grain number and weight. The results highlighted the role these enzymes to change the source-sink balance in wheat, which could be used as bio-signatures for breeding and selection of drought-resilient genotypes for a future drier climate. In experiment III, to understand the effect of the CO2 concentration on plant growth, its interaction with heat stress, and to study the role of an isoflavone reductase-like gene in conferring heat stress tolerance, we characterized two near-isogenic wheat genotypes with contrasting yield potential under heat stress. Heat stress significantly affected physiological parameters such as photosynthetic rate (An), chlorophyll fluorescence (Fv/Fm), phytohormone levels and antioxidant enzyme activities in leaves. Many of these physiological parameters were shown to correlate with each other in response to heat regardless of the genotypes. Furthermore, they correlated with plant biomass pot-1 (B) and grain yield pot-1 (GY), which were reduced by heat. Overall, the maintenance of the redox homeostasis appeared to be crucial for the adaptation of wheat to heat by interacting with ABA and CKs. Furthermore, a lower gene expression of isoflavone reductase (IR)-like in LB genotypes under normal conditions and under elevated CO2 indicating its role in heat adaptation however, further experimentation is required to validate our findings. The coda of our studies suggests that transgressed genetic diversity from synthetics and landraces has the potential to improve drought and heat tolerance of spring wheat genotypes. And, a number of physiological and biochemical traits associated with ABA and CKS can be selected for breeding resilient wheat cultivars suitable for hot and dry environments in future climate change scenarios.