To develop a medium-entropy alloy (MEA) with a high yield strength at temperatures ranging from cryogenic (-196 ℃) to elevated (800 ℃) temperatures, a strategy for strengthening nanoparticle precipitation while reducing the MEA stacking fault energy (SFE) is proposed. A novel Ni2CoCrNb0.2V0.2 MEA suitable for additive manufacturing (AM) was designed according to the first-principles calculations and the calculation of phase diagrams (CALPHAD) technique. Bulk MEA samples were printed using laser-directed energy deposition (LDED) with a vibration field. First-principles calculations indicated that V addition could reduce the SFE and stabilize the γ′′ strengthening phase. The aged MEA had excellent yield strengths of ∼1398MPa and ∼751MPa at -196 ℃ and 650 ℃, respectively. The specific strength of the MEA reached 94.16MPag−1 cm−3 at 650 ℃. The deformational mechanism transforms from stacking fault (SF), deformation twin (DT), and Lomer–Cottrell (L-C) lock synergy to slip-dominated plasticity when the tensile temperature increases from -196 ℃ to 800 ℃. This research provides new theoretical guidance for developing AM-ed MEAs with an ultrastrong combination of strength and ductility for extreme temperatures applications.