<p>Electron beam directed energy deposition (EB-DED) is a promising technique for multi-material additive manufacturing (AM) due to material compatibility and rapid build rates. However, combining dissimilar metals in AM remains challenging because of differences in thermal properties and the formation of unwanted secondary phases at the interface. In this study, EB-DED was used to deposit austenitic stainless steel and vanadium to determine compatibility between this metal combination and the manufacturing process. By systematically mapping the processing window of the EB-DED system, parameter sets were identified that yielded defect-free deposits. Additionally, detailed characterization of cracked deposits showed that failure was often driven by the solid-state transformation to the sigma phase intermetallic compound. Using computational thermodynamic tools, the composition range where this transformation occurs in the multicomponent SS-V system was identified. These computational predictions closely match experimental observations and provide insight into the thresholds between different failure morphologies. As the demand for multi-material AM components grows, the approach taken in this study, integrating rapid combinatorial experiments and computational tools, provides an efficient new method for designing future dissimilar metal DED processes.</p>