The interaction of nanoparticles (NPs) with proteins forms a dynamic nanoparticle-protein corona (NP-PC), which significantly influences the biological reactivity of NPs. This review highlights the factors affecting NP-PC formation, including NP composition, surface characteristics, and protein properties. The NP-PC can alter the structure and function of adsorbed proteins, leading to changes in cellular uptake, inflammation, and clearance. Understanding these interactions is crucial for developing bio-compatible nanomaterials with controlled surface properties. The review also discusses the implications of NP-PC on cellular interactions, such as phagocytosis, macropinocytosis, and endocytosis, and the role of serum proteins in these processes. Additionally, it explores analytical techniques for studying NP-protein interactions, emphasizing the importance of characterizing the NP-PC to predict the biological effects of NPs.The interaction of nanoparticles (NPs) with proteins forms a dynamic nanoparticle-protein corona (NP-PC), which significantly influences the biological reactivity of NPs. This review highlights the factors affecting NP-PC formation, including NP composition, surface characteristics, and protein properties. The NP-PC can alter the structure and function of adsorbed proteins, leading to changes in cellular uptake, inflammation, and clearance. Understanding these interactions is crucial for developing bio-compatible nanomaterials with controlled surface properties. The review also discusses the implications of NP-PC on cellular interactions, such as phagocytosis, macropinocytosis, and endocytosis, and the role of serum proteins in these processes. Additionally, it explores analytical techniques for studying NP-protein interactions, emphasizing the importance of characterizing the NP-PC to predict the biological effects of NPs.