Thermoelectric (TE) devices are able to convert heat flux into electrical power and are, therefore, of utmost technological importance. Our goal is to manipulate the microstructure of TE materials to optimize their conversion efficiency. We process both single-phase TE materials with different solid-solution forming elements and two-phase TE alloys comprising matrix and precipitates, supplemented by ab-initio calculations as guidelines for the design process. Employing advanced characterization techniques, we analyze the materials structure and chemistry down to the nanometer length-scale, as well as their TE properties. This enables us drawing the correlation between the microstructure and TE performance of materials.