The large strength difference between soft and hard zones in heterostructured materials is a double-edged sword: on the one hand, the effective back () and forward stress () are generated to produce hetero-deformation induced (HDI) strengthening and strain hardening effect. On the other hand, the micro-cracks tend to initiate and propagate along the interface to cause premature failure. Here we prepared three different heterostructured Ti-4.8Al-5.6Mo-3V-1.5Cr-1.6Fe alloys to reveal the influence of magnitude of strength difference between soft primary α phase (αp) and hard β matrix on its tensile strength and ductility. It demonstrates that only when the sum of applied stress () and is greater than the yield strength of hard β matrix (), i.e., , the alloy can obtain both high strength and ductility. Contrary, when , the alloy exhibits a highest strength but a lowest ductility. These findings are expected to help with designing heterostructured materials for superior mechanical properties.