AbstractThe fabrication of novel systems where enzymatic and metallic actives sites directly interact represents an elegant strategy for sustainable processes. One of the new strategies involves the in situ formation of metal nanoparticles on a protein network as scaffold. This biological entity is the key element because it conserves the biological catalytic efficiency and induces the final metallic nanoparticles generation on the structure. This method allows to obtain bifunctional enzyme‐metallic catalysts with excellent versatility and efficiency in a different reaction and experimental conditions. In this concept article, the relevant aspects in terms of fabrication of enzyme‐metal nanoparticles hybrids and recently reported examples of successful application in cascade processes will be described.