Mulberry sericulture contributes 75% of silk production in the country and the fully domesticated Bombyx mori L. solely depends on mulberry leaves for its nutrition. Under the present scenario of changing climate, it has become utmost important for the sericulture scientists to increase the yield potential of mulberry crop for sustaining the sericulture industry, when the non-mulberry, non-domesticated and semi-domesticated silkworms are more vulnerable to climate vagaries and poses greater risk to sustenance. Physiological and molecular breeding strategies which are successful in other crops can be adapted in mulberry for improving leaf yield and quality to increase silk production per unit area. Collaborative efforts are required from breeders and physiologist to bridge the gap and understand the complex traits in mulberry for addressing abiotic and biotic stress causing huge crop loses. The scope of molecular breeding in mapping the relevant physiological traits and the potentials of gene editing in developing climate-resilient mulberry varieties must be explored. This chapter discusses the present scenario and future strategies for yield enhancement in mulberry considering trait-driven physiological breeding approaches for combating climate change.