The synergistic impact of nanomaterials is critical for novel intracellular and/or subcellular drug delivery systems of minimal toxicity. This synergism results in a fundamental bio/nano interface interaction, which is discussed in terms of nanoparticle translocation, outer wrapping, embedding, and interior cellular attachment. The morphology, size, surface area, ligand chemistry and charge of nanoparticles all play a role in translocation. In this review, we suggest a generalized mechanism to characterize the bio/nano interface, as we discuss the synergistic interaction between nanoparticles and cells, tissues, and other biological systems. Novel perceptions are reviewed regarding the ability of nanoparticles to improve hybrid nanocarriers with homogeneous structures to enhance multifunctional biomedical applications, such as bioimaging, tissue engineering, immunotherapy, and phototherapy.