This paper presents the novel microstructure design, called Harmonic Structure, which gives structural metallic materials outstanding mechanical properties through an innovative powder metallurgy process. Homogeneous and ultra-fine grain (UFG) structure enables the materials high strength. However, such a “Homo-“ and “UFG” microstructure does not, usually, satisfy the need to be both strong and ductile, due to the plastic instability in the early stage of the deformation. As opposed to such a “Homo-and UFG“ microstructure, “Harmonic Structure” has a heterogeneous microstructure consisting of bimodal grain size together with a controlled and specific topological distribution of fine and coarse grains. In other words, the harmonic structure is heterogeneous on micro-but homogeneous on macro-scales. In the present work, the harmonic structure design has been applied to pure metals and alloys via a powder metallurgy route consisting of controlled severe plastic deformation of the corresponding powders by mechanical milling or high pressure gas milling, and subsequent consolidation by SPS. At a macro-scale, the harmonic structure materials exhibited superior combination of strength and ductility as compared to their homogeneous microstructure counterparts. This behavior was essentially related to the ability of the harmonic structure to promote the uniform distribution of strain during plastic deformation, leading to improved mechanical properties by avoiding or delaying localized plastic instability.