The key obstacles to developing high performance polymer nanocomposites are poor dispersion of the nanomaterial in the polymer matrix and weak interfacial interactions. Overcoming these obstacles require understanding structure-processing-property interrelationships. Design of Experiments (DOE) was used to evaluate the interrelationships between initial nanomaterial-polymer incorporation, nanomaterial chemistry and extrusion processing conditions on the rheological and thermal properties of nanocomposites. Using either dry mixing or solvent intercalation, 1 vol. % SWNTs, VGCF, and C12-SWNTs were added to 12 MFI polypropylene (PP) and melt extruded. The extruder was a Haake MiniLab counter-rotating twin screw extruder with a recirculation channel to enable multiple passes. The control variables were extrusion temperature, screw speed, and total residence time. The response variables included pressure drop (an indication of relative viscosity), melting point, crystallization temperature and the onset of thermal decomposition. As expected, even after extrusion, solvent intercalation gave a better dispersion and therefore better properties than dry mixing. However, it was found that long residence times and high screw speeds were not necessarily desirable for improving properties. For example, the properties of the VGCF-PP nanocomposite clearly degraded with long recirculation times. In addition, it was found that while the time and screw speed are coupled in terms of the total number of passes, they had independent contributions to the nanocomposite properties. The material with the highest thermal decomposition temperature was strongly dependent on the processing conditions and the optimum processing condition was different for the different materials. These results demonstrate that developing high performance thermoplastic nanocomposites requires a holistic approach that addresses the combination of initial blending, chemistry, and melt processing as well as the effectiveness of using design of experiments to elucidate structure-processing-property interrelationships.