Synchronous improvement of strength and ductility is a challenging and longstanding problem in the further development and engineering applications of titanium matrix composites (TMCs). In this study, we designed a novel heterogeneously optimized TMC for the first time, which features fine grain/coarse grain (FG/CG) regions embedding in-situ interfacial submicron-TiB/micron-TiC and intragranular nano-TiB whiskers. The TMCs achieved a strength-ductility combination, representing a nearly 30% increase without any reduction in ductility compared with the matrix alloy. The bimodal structures of the TMCs, as well as the micro-nano reinforcements and their interfacial/intragranular distribution, play a predominant role on the strengthening-toughening effect. Besides, the various dislocation behaviors including multiple slips, slip transmission across grain boundaries and activation of more 〈c + a〉 dislocations near the reinforcements, contribute to the desirable ductility. These findings highlight the untapped potential for improving mechanical properties of metal matrix composites.