The increasing integration of engineered nanoparticles into human and environmental contexts parallels the rapid advancement of nanotechnology. Nanoparticles interact with membranes, cells, DNA, and organelles through colloidal forces and dynamic biophysiochemical interactions, forming diverse nanoparticle/biological interfaces. Revolutionary nanosystems have demonstrated significant potential in monitoring and safeguarding biological systems. The concept of nano-bio interfaces has become feasible through the rapid progress in integrating biological entities with programmable nanomaterials. However, challenges such as potential toxicity, immunogenicity, and reduced efficacy hinder the widespread biomedical application of nanomaterials. Understanding the intricate relationships within nano-bio interactions remains incomplete, limiting the clinical effectiveness of nanomedicines. Despite these challenges, nanomaterials exhibit immense promise as powerful diagnostic and therapeutic tools in various nanomedicine applications. Harnessing the exceptional magnetic, optical, and photothermal properties of inorganic nanoparticles for multifunctional molecular imaging necessitates engineering them with a biocompatible shell to optimize their physicochemical characteristics.