Conventional particle reinforced titanium matrix composites (TMCs) often suffer from a strength-ductility trade-off, primarily due to inadequate interfacial bonding and microstructural inhomogeneity. To overcome this problem, this study developed a novel strategy combining cold spray-friction stir processing composite additive manufacturing (CFAM) with high-entropy alloy (HEA) reinforced particles to synergistically optimize both interfacial performance and microstructure uniformity. The results showed that, compared to cold spray additive manufacturing (CSAM), CFAM not only completely eliminated internal pores and cracks but also significantly refined the average matrix grain size from 5.0 μm to 2.6 μm through dynamic recrystallization and the Zener pinning effect, while achieving a uniform distribution of HEA particles. Furthermore, CFAM transformed the localized and incoherent interfaces into a continuous semi-coherent interfacial architecture composed of a new HEA solid-solution layer and a β-Ti phase layer. This interface exhibited mechanical properties intermediate between the matrix and HEA particles, thereby mitigating stress concentration and facilitating strain transfer. The synergistic effect of the fine-grained matrix, the mechanically graded interface, and the uniformly distributed HEA particles yielded an outstanding combination of tensile strength (924 MPa), yield strength (737 MPa), and elongation (8.2%). This work provides a new preparation strategy for developing high-performance TMCs.