III in paprika powder, [ 11 ] azorubine in drinks, [ 12 ] or melamine in milk. [ 13 ] In clinical application schemes, SERS shows high potential as a point-of-care method for the online monitoring of morphine, methadone, or dopamine [ 14 ] in intravenous delivery tubing or of levofl oxacin in urine. [ 15 ] Moreover, the detection of environmentally relevant and harmful substances, i.e., arsenic (III) in lake water samples [ 16 ] or veterinary drugs such as metronidazole and ronidazole in various water sources, [ 17 ] extends the application fi eld of SERS. All of the above-mentioned application examples share the enhancement of the naturally weak Raman signal by employing nanostructured metal surfaces, so-called SERS substrates.The applied nanostructured SERS substrates are commonly generated via wet chemistry [ 18 ] and bottom-up [ 19 ] or topdown [ 20,21 ] approaches. Metal colloids can be prepared in large quantities via wet chemical reactions, e.g., the reduction of silver or gold salts to the pure metal. In general, metallic nanoparticle suspensions are characterized by easy handling and fast production in high quantities. In contrast, limitations are related to their low time stability, poor batch-to-batch reproducibility, and spectral interference originating from the reaction participants. As an alternative, laser ablation techniques are employed to fabricate metal nanoparticles without stabilization agents on their surfaces. [ 22 ] Moreover, planar substrates produced by immobilization of metallic nanoparticles based on a bottom-up technique are characterized by low homogeneity across a large area and low batch-to-batch quality.Top-down techniques can overcome some of the above-mentioned limitations by structuring thin metal layers using lithographic techniques, e.g., electron beam lithography (EBL) [ 21,23 ] or nanoimprint lithography (NIL). [ 24 ] These procedures lead to highly homogenous planar substrates with well-defi ned structures and plasmonic resonance tunabilities. However, due to the multiple processing steps required for top-down techniques, the manufacturing time for a given structure is extensive and the process is expensive. Thus, the top-down production of SERS active substrates is realized in small quantities.By an appropriate combination of bottom-up and top-down techniques, the creation of a SERS active substrate that uses the advantages and avoids the drawbacks of each applied fabrication technique becomes feasible. In principle, a sophisticated top-down approach is improved by a fast and easy bottom-up method. As an example, particle-in-cavity structures [ 25 ] were created for which the template (the cavity structure) is fabricated by nanosphere lithography (NSL) [ 25 ] following a porous By combining a bottom-up process with top-down fabricated templates, the benefi ts of both methods are joined by creating so-called TopUp plasmonic arrays for surface-enhanced Raman spectroscopy (SERS). The morphological and optical characterization of the TopUp substrates illustrates exceptional...