Multi-material additive manufacturing offers new opportunities for tailoring local material performance, but reliable design principles for joining dissimilar materials with large thermophysical mismatch remain limited. Binder-jetted WC-Co substrates were combined with electron beam powder bed fusion deposited 316L stainless steel to investigate structure − property relationships governing interfacial integrity. Microstructural characterization revealed bidirectional elemental diffusion (Fe, Cr, Ni, Co, and W) across the interface and formation of a chemically graded transition region with a thickness of approximately 144–204 µm depending on processing parameters. X-ray diffraction confirmed retention of the primary phases together with minor secondary phase formation, while nanoindentation mapping demonstrated a continuous gradient in hardness and elastic modulus across the interface rather than a mechanically weak layer. Despite the formation of a mechanically continuous interface, cracking occurred within the WC-Co substrate, which is consistent with thermally induced stresses arising from the mismatch in coefficients of thermal expansion between WC-Co and 316L. These results suggest that interfacial reactions can enhance interfacial integrity even in systems with large property mismatch, shifting failure away from the interface and into the weaker constituent. The findings provide design insight for engineering robust interfaces in multi-material additive manufacturing systems combining ductile alloys with brittle composites.