Nanopores are nanochannels formed through thin insulating membranes such as silicon nitride, and are powerful, yet conceptually and structurally simple, single-molecule sensor elements. When immersed in an electrolyte and with a cross-membrane applied voltage, the presence of a target species is indicated, in a resistive-pulse-sensing mode, by a perturbation of the ionic current through the pore whose frequency is correlated to the analyte concentration, and whose characteristics relate to the analyte, solution, and nanopore properties. It is important to be able to tune the nanopore size and surface properties; we present low-overhead routes based on electroless plating to fabricated customized nanopores. Those fabrication strategies can augment the performance capabilities of channel-through-membrane devices, but are also useful in combination with other structures and applications. In particular, we have used the same core electroless plating approach to turn a wide variety of materials into substrates for surface-enhanced Raman spectroscopy (SERS). These materials span from conventional micro- and nanofabrication-compatible materials, whether native or highly structured, to consumer-scale materials such as paper. These materials can, by their properties and construction, offer chemical analysis capabilities that complement the added SERS performance. In the case of paper-based SERS, an added benefit is the natural compatibility with the demands of low-cost diagnostics, including ease of disposability. Details of nanofabrication strategies will provide context for discussion of prospects of, and concrete biosensing applications using, tailored nanopore single-molecule sensors and multifunctional SERS substrates. Practical issues affecting device ease of use and sensing performance will be outlined, extending to disposable devices.