A study of the interfacial properties of Ni-Al-V alloys is presented further, together with the interatomic potentials of the Ni-Al-V ternary phase system given in this paper, with the application of the Phase-field method and atomistic simulations, based on the second nearest-neighbor modified embedded-atom method (2NN MEAM) potential formalism. It is discovered that the alloy elements have different preferences of segregation or depletion at the (100) FCC/L12 interface (the γ-FCC-Ni(Al, V) and the L12-Ni3(Al, V)) of diffusion phases. Nickel atoms segregate first and then deplete, Vanadium atoms segregate while aluminum atoms deplete at the (100) FCC/L12 interfaces forming new diffusion phases. Both, vanadium segregation and aluminum depletion affect the alloy’s interfacial properties which in turn, will lower the interfacial energy and increase the work of separation. The results of the Phase-field method coincide with the results of the atomistic computation based on the 2NN MEAM method. Furthermore, the applicability of the atomistic approach to an elaborate alloy design of advanced Ni-based superalloys through the investigation of the effect of alloying elements at the interfacial properties is discussed.