Bread wheat is one of the major global cereal crops. However, sustainable wheat production is threatened by several stresses including salinity, drought, and high temperature stresses. Drought and heat stresses often occur together and cause substantial reduction in grain yield. This study was conducted to evaluate the potential of seed priming with nano chitosan-glycinebetaine in improving the tolerance against combined heat and drought stresses in two bread wheat (Triticum aestivum L.) genotypes Annaj-2017 and TW1509. For priming, the seeds of wheat genotypes were soaked in aerated distilled water (hydropriming) or nano-sized chitosan-glycinebetaine solution (100 mM) for 18 h. The seeds (six seeds per pot) were sown in plastic pots filled with Universal potting media (2.5 kg per pot) maintained at 70% water holding capacity (WHC). Two weeks after sowing, pots were divided into four groups viz. (i.) 70% WHC at 25/18 +/- 2 degrees C (control), (ii.) 35% WHC at 25/18 +/- 2 degrees C (drought stress), (iii.) 70% WHC at 37/28 +/- 2 degrees C (heat stress), and (iv.) 35% WHC at 37/28 +/- 2 degrees C (heat stress). Heat and drought stresses and their combinations caused a significant reduction in growth and grain yield through stress-induced oxidative damages, stomatal alternations causing a decline in carbon influx, and metabolic disruptions. However, the effect of combined drought and heat stresses was more devastating effects than individual heat and drought stresses. Seed priming with nano-sized chitosan-glycinebetaine improved the growth, grain development, and yield formation in both tested bread wheat genotypes Annaj-2017 and TW1509 under individual and combined stresses. This improvement was attributed to tissue water conservation, accumulation of osmolytes, like glycinebetaine and proline, and increase in the activities of antioxidant enzymes, which aided to scavenge the stress-induced oxidative damages and sustain carbon influx and assimilation and grain development. Seed priming with nano-sized chitosan-glycinebetaine improved heat and drought tolerance in wheat genotypes through osmotic adjustment, tissue water conservation, activation of the antioxidant defense system, a continuation of carbon assimilation, and activities of grain-filling enzymes which sustained plant growth and yield formation.