Multi-material additive manufacturing opens a new avenue for materials design and synthesis, but also increases the complexity in the process-structure-property relationships. To this end, we have developed and seamlessly integrated a series of high-fidelity multi-physics models for multi-material additive manufacturing. Specifically, multiphase flow models using the coupled computational fluid dynamics (CFD) and discrete element method (DEM) simulate the motions of unmelted powder particles in the melting procedure of nano- and micro-particle reinforced composites [1]. For the cases where different powders are melted for in-situ alloying, the model incorporates the major physical factors, e.g., the composition evolution due to evaporation and convection, the varying thermo-physical material properties dependent on the local chemical compositions, and the heat release/absorption due to alloying/chemical reactions [2]. The microstructure evolutions at both the grain- and dendrite- scales are modelled using the phase field and cellular automaton methods. The mechanical properties and thermal stresses are simulated using the crystal plasticity finite element (FE) model, which incorporates the realistic geometry (rough surfaces and voids), temperature profiles and microstructures including the interactions between reinforcing particles and dislocations. These models have proven to be useful in revealing the physical mechanisms and guiding manufacturing process optimization, which have been validated against experiments.