This dissertation focuses on the development of a unique microfluidic approach, using hydrodynamic focusing, to enable both surface enhanced Raman scattering (SERS) and electrochemical characterization of analytes at nanomolar concentration in flow. The approach utilizes a versatile polystyrene chip that contains an encapsulated microelectrode and fluidic tubing with a polydimethylsiloxane (PDMS) microchannel positioned over both to generate a sheath-flow that confines and increase the interaction between the analyte and the surface to improve detection. The microfluidic device was characterized using finite element simulations, amperometry, and Raman experiments. An examination of riboflavin (vitamin B12) and catechol demonstrated a SERS and amperometric detection limit near 1 and 25 nM, respectively. This combination of SERS and amperometry in a single device provides an improved method to identify and quantify electroactive analytes over either technique independently. The platform has also been used to investigate the role of surface adsorption in the SERS and electrochemical detection of neurotransmitters, as well as examine reversible changes in spectral features of riboflavin based on applied potential.