Reducible metal oxide nanozymes (rNZs) have been a subject of intense recent interest due to their catalytic nature, ease of synthesis, and complex surface character. Such materials contain surface sites which facilitate enzyme‐mimetic reactions via substrate coordination and redox cycling. Further, these surface reactive sites have been shown to be highly sensitive to stresses within the nanomaterial lattice, the physicochemical environment, and to processing conditions occurring as part of their syntheses. When administered in vivo, a complex protein corona binds to the surface, redefining its biological identity and subsequent interactions within the biological system. Catalytic activities of rNZs each deliver a differing impact on protein corona formation, its composition, and in turn, their recognition, and internalization by host cells. Improving our understanding of the precise principles that dominate rNZ surface‐biomolecule adsorption raises the question of whether designer rNZs can be engineered to prevent corona formation, or indeed to produce “custom” protein coronas applied either in vitro, and pre‐administration, or formed immediately upon their exposure to body fluids. Here, we consider fundamental surface chemistry processes and their implications in rNZ material performance. In particular, we discuss material structures which inform component adsorption from the application environment, including substrates for enzyme‐mimetic reactions.This article is protected by copyright. All rights reserved