Abstract: Nanostructured multiphase (NM) alloys have attracted extensive attention due to their superior mechanical properties. However, it is still a great challenge to effectively design and produce large-scale NM alloys. Here, utilizing the intermediate-temperature instability of high entropy alloys (HEAs), we propose a new approach to rapidly design and effectively produce bulk NM alloys. The key to our design approach includes the “destabilization strategy” to destabilize the single-phase HEA, and the “self-optimization” strategy to rapidly identify the composition of NM alloys. We developed a bulk NM alloy with a hardness of up to ∼1378 HV. Such a high hardness originates from a two-stage phase decomposition behaviour at intermediate temperatures and the formation of a unique coherent multiphasic nanostructure. This design strategy not only effectively guides the discovery of novel NM alloys from the immense compositional space of HEAs, but also enables the large-scale synthesis of NM alloys.