Precipitation-strengthened medium/high-entropy alloys (MEAs/HEAs) have great potential for high-temperature applications. In this study, we designed a novel Ni45.9Fe23Cr23V4Nb3Mo1B0.1 (at.%) MEA alloy, hardened by the D022 (Ni, Fe, Cr)3(Nb, V)-type nanoprecipitates, with an excellent strength-ductility combination from room to elevated temperatures. Specifically, the tensile strengths, at 700 and 800 °C, could be maintained as high as 845 and 589 MPa, respectively; meanwhile, elongations at all testing temperatures exceeded 25 % without any intermediate-temperature embrittlement. The temperature-dependent deformation mechanisms were unraveled using multi-scale characterizations, which involved profound slip planarities, such as stacking fault (SF) networks and deformation twins (DTs). Furthermore, the critical resolved shear stress (CRSS) to initiate SFs in both face-centered cubic (FCC) and D022 phases was evaluated, and the possible reasons for the origin of anomalous DTs at 800 °C were discussed in detail. The main findings demonstrate that the shearable D022 nanoparticles can provide the FCC matrix with considerable dislocation storage capacity, reinforcing strain hardening at ambient and intermediate temperatures. This work provides fundamental insights into the controllable design and deformation mechanisms of high-performance D022-strengthened MEAs/HEAs.