This article is the first to apply wire-feed electron beam additive manufacturing in vacuum to fabricate a part from a complex nickel-based superalloy with directional structure on a stainless steel substrate. It is shown that the determining factor for the formation of parts with directional structure is the local metallurgy conditions implemented in electron beam additive manufacturing. These conditions are the magnitude and direction of the temperature gradient as well as the geometry (shape) of the solidification front in the molten pool. The substrate effect (both chemical and structural) on the composition and structure of the part material is cancelled out at a distance not exceeding 8.0 mm from the substrate. Thus, the proposed 3D printing method is quite acceptable for the manufacturing of parts from heat-resistant nickel alloys with directional structure on substrates made of less expensive materials.