Directed energy deposition (DED) is an efficient method to fabricate functionally graded materials (FGMs) with gradient composition and complex structures, allowing for local tailoring of properties instead of the costly need for extraneous welds and joints. In this study, a FGM from stainless steel to Inconel alloy was successfully fabricated using the powder-based laser DED. A very refined grain structure has been observed in at the composition with 75 wt.% Inconel alloy content, which also exhibits the highest (entropy). For the first time, the post heat treatments, microstructure and aging precipitation behaviors of FGMs were systematically studied via experimental characterization and computation, to elucidate their effects on the gradient smoothing and mechanical properties. The diffusion and segregation of Ni, Nb and Ti elements underly the transformation mechanism between Laves, δ, γ’ and γ’’ phases during precipitation. Homogenization on FGMs not only eliminates the heterogeneity inherited from the AM process, but also provides a practical way to smoothen the gradient on composition and microstructure for the eventual good gradient properties. It has a direct influence on the following precipitation behaviors in the FGM, which highly relies on the diffusion degree of the elements in the matrix and grain boundaries. The high-throughput thermodynamic modeling and kinetic modeling were exploited to evaluate the experimental microstructure and address computational uncertainty using different thermodynamic conditions and databases, which enables an accelerated design through local tailoring of process-structure-property relationships to develop new functional materials.