Recent developments in nanoplasmonic sensors promise highly sensitive detection of chemical and biomolecular analytes with quick response times, affordable costs, and miniaturized device footprints. These include plasmonic sensors that transduce analyte-dependent changes to localized refractive index, vibrational Raman signatures, or fluorescence intensities at the sensor interface. One of the key challenges, however, remains in producing such sensors reliably, at low cost, using manufacturing compatible techniques. In this chapter, we demonstrate an approach based on molecular self-assembly to deliver wafer-level fabrication of nanoplasmonic interfaces, with spatial resolutions down to a few nanometers, assuring high quality and low costs. The approach permits systematic variation to different geometric variables independent of each other, allowing the significant opportunity for the rational design of nanoplasmonic sensors. The ability to detect small molecules by SERS-based plasmonic sensing is compared across different types of metal nanostructures including arrays of nanoparticle clusters, nanopillars, and nanorod and nanodiscs of gold.