Protein interactions at polymer interfaces represent a complex but ubiquitous phenomenon that demands an entirely different focus of investigation than what has been attempted before. With the advancement of nanoscience and nanotechnology, the nature of polymer materials interfacing proteins has evolved to exhibit greater chemical intricacy and smaller physical dimensions. Existing knowledge built from studying the interaction of macroscopic, chemically alike surfaces with an ensemble of protein molecules cannot be simply carried over to nanoscale protein-polymer interactions. In this Perspective, novel protein interaction phenomena driven by the presence of nanoscale polymer interfaces are discussed. Being able to discern discrete protein interaction events via simple visualization was crucial to attaining the much needed, direct experimental evidence of protein-polymer interactions at the single biomolecule level. Spatial and temporal tracking of particular proteins at specific polymer interfaces was made possible by resolving individual proteins simultaneously with those polymer nanodomains responsible for the protein interactions. Therefore, such single biomolecule level approaches taken to examine protein-polymer interaction mark a big departure from the mainstream approaches of collecting indirectly observed, ensemble-averaged protein signals on chemically simple substrates. Spearheading research efforts so far has led to inspiring initial discoveries of protein interaction mechanisms and kinetics that are entirely unique to nanoscale polymer systems. They include protein self-assembly/packing characteristics, protein-polymer interaction mechanisms/kinetics, and various protein functionalities on polymer nanoconstructs. The promising beginning and future of nanoscale protein-polymer research endeavors are presented in this article.