Surface enhanced Raman spectroscopy (SERS) is an attractive tool in analytical sciences dueto its high specificity and sensitivity. Since the SERS active substrates are only available as 2Darrays, the fabrication of 3D nanostructures allows for an increased number of hot spots inthe focus volume, thus further amplifying the SERS signal. Although a great number offabrication strategies for powerful SERS substrates exist, the generation of 3Dnanostructures with high complexity and periodicity is still challenging. For this purpose, wereport an easy fabrication technique for 3D nanostructures following a bottom-uppreparation protocol. Enzymatically generated silver nanoparticles (EGNPs) are prepared,and the growth of hierarchically designed 3D flower-like silica-silver compositenanostructures is induced by applying plasma-enhanced atomic layer deposition (PE-ALD) onthe EGNPs. The morphology of these nanocomposites can be varied by mostly changes in thePE-ALD cycle number, and a flower height up to 10 μm is found. Moreover, the metallized(e.g., silver or gold) 3D nanostructures resulting from 135 PE-ALD cycles of silica creationprovide highly reproducible SERS signals across the hydrophobic surface. Within thiscontribution, the morphological studies, optical properties as well as the SERS response ofthese metallized silica-silver composite nanostructures applying vitamin B2 as a modelanalyte is introduced.