Technological innovations in biomaterial sciences harness nanoparticle (NP) production, manipulation, and deposition with supreme precision, enabling the development of industrial processes. This review first discusses the basic components of this approach, introducing cluster sources, experimental apparatus, and growth mechanisms for NP formation. The second part of this review provides an overview of how the nanoscale bottom-up engineering can control protein adsorption, which in turn determines the fate of nanostructured coating for prokaryotic and mammalian (primary and stem) cell interactions. In addition, we briefly address the implications of the cluster beam deposition technique for nanostructuration of biocompatible microdevices and its potential as a facile coating method to promote protein-surface interactions for microarray applications in biotechnology.