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Bionanotechnology has developed rapidly over the past two decades, owing to the extensive and versatile, functionalities and applicability of nanoparticles (NPs). Fifty-one nanomedicines have been approved by FDA since 1995, out of the many NPs based formulations developed to date. The general conformation of NPs consists of a core with ligands coating their surface, that stabilizes them and provides them with added functionalities. The physicochemical properties, especially the surface composition of NPs influence their bio-interactions to a large extent. This review discusses recent studies that help understand the nano-bio interactions of iron oxide and gold NPs with different surface compositions. We discuss the influence of the experimental factors on the outcome of the studies and, thus, the importance of standardization in the field of nanotechnology. Recent studies suggest that with careful selection of experimental parameters, it is possible to improve the positive correlation between in vitro and in vivo studies. This provides a fundamental understanding of the NPs which helps in assessing their potential toxic side effects and may aid in manipulating them further to improve their biocompatibility and biosafety. Image 1 • Inorganic/metallic core nanoparticles comprise 25% of the nanomedicines in clinical trials. • Nano-bio interactions are complex and lack of standardization in the field further limits their transition to clinical trials and beyond. • Experimental parameters play an important role along with the nanoparticle physicochemical properties in understanding their net effect on a biological system. • Standardization will aid in making fair and relevant comparisons between studies, correlate in vitro and in vivo studies better and may help towards achieving the goal of reduce, refine and replace. [ABSTRACT FROM AUTHOR]