Extreme weather including heat waves and drought episodes are expected to increase in intensity and duration due to climate change. Wheat, being a major crop is under extreme threat to these stresses especially at the reproductive stage. This review addresses the potential of diverse wheat germplasm (originated from landraces and synthetic derivatives) to cope with drought and heat stress at the flowering stage. Here, important marker-trait associations were reported for sustainable grain production under drought and heat stress at anthesis. Likewise, the mechanisms of drought and heat resilience including gene expression and physiological traits (activities of carbohydrate metabolic and antioxidant enzymes, and endogenous hormonal responses) were explored. These studies helped to understand the genetic and physiological basis of drought and heat tolerance and certain pre-breeding traits related to osmotic adjustment, phytohormonal regulation, antioxidant metabolism, and the expression of novel genes were identified. Moreover, identified pre-breeding traits and genotypes can be utilized in breeding wheat cultivars resilient to future adverse environments.