Misfit strain relaxation-induced morphology instability is usually observed in epitaxial heterostructures at high temperatures. In this paper, we report that this morphology instability can occur even at room temperature in epitaxial ZnO/AZO (Al-doped ZnO) core-shell nanowires (NWs). As a result, densely distributed ZnO nanodots (NDs) were self-assembled on the NWs. The growth of NDs was slowed down during aging owing to the gradually reduced misfit strain. The final size and shape of the NDs were highly depended on the shell thickness and the doping ratio. It was proved that the morphology stability could be improved by surface passivation, thinning the shell thickness, or lowering the doping ratio. The results may provide instructive suggestions for the reliable design in strain and surface engineering of nanomaterials.