Graphene Oxide (GO) is known to impart enhanced mechanical behavior on polymer composites, but serious challenges remain that has prevented these composites from reaching their full potential, such as the inability to process them at large scales, e.g., through compounding via twin-screw extrusion, while simultaneously achieving significant improvements in the mechanical properties, due to the difficulties in preventing exfoliated GO nanosheets from re-agglomerating upon processing and in inducing adequate levels of adhesion to the matrix polymer. Thermoplastic polyurethanes (TPUs) are multi-block copolymers consisting of hard and soft segments. The former (HS) are most often thermodynamically incompatible with the ltter and phase separation occurs, with HSs forming domains that consist in either glassy or semi-crystalline regions that act as physical cross-links and provide stiffness and reinforcement, which makes them prime candidates for polymer/GO nanocomposites. In this work we show that by: i) An adequate choice of GO functionalization and exfoliation; ii) The use of TPUs with the adequate structure, as determined by mesoscale computational simulations; iii) Processing using recently developed special mixing equipment that imparts extensional-dominated mixing upon extrusion instead of the most common shear-dominated mixing, it is possible to design and produce nanocomposites with much enhanced mechanical properties, e.g., significant increases in modulus and abrasion resistance, while also increasing strain at rupture.