In the present paper, the interrelated aspects of additive manufacturing-microstructure-property in directed energy deposition of SS316L-IN718 multi-material were studied through numerical modeling and experimental evaluation. The printability concept and solidification principles were used for this purpose. The printability analysis showed that the SS316L section is more susceptible to composition change and lack of fusion, respectively due to the high equilibrium vapor pressure of manganese and the more efficient heat loss in the initial layers. However, the IN718 section is more prone to distortion due to the formation of a larger melt pool, with a maximum thermal strain of 3.95 × 10−3 in the last layer. As the process continues, due to heat accumulation and extension of the melt pool, the cooling rate decreases and the undercooling level increases, which respectively result in coarser microstructure and more instability of solidification front in the build direction, as also observed in the experimental results. The difference is that the dendritic microstructure of the IN718 section, due to the eutectic reaction L → γ + Laves, is formed on a smaller scale compared to the cellular microstructure of the SS316L section. Also, the decrease in cooling rate caused the secondary phase fraction in each section (delta ferrite in SS316L and Laves in IN718) to increase almost linearly. However, the hardness calculation and measurement showed similarly, even though with the transition from SS316L to IN718 the hardness is significantly increased due to higher yield strength of the matrix and the presence of Laves intermetallic phase (~ 260 HV0.3), the hardness in each section decreases slightly due to the coarsening of the microstructure from the initial layer to the final.