Microfluidics technology promises to advance many current areas of research including point-of-care diagnostics and cell-based assays. However, there is a need to address current challenges associated with the iterative design and fabrication process of microfluidic systems in thermoplastics that are amenable to mass production downstream. The objective of this study was to develop an optimized fabrication approach that will enable medium volume production of microfluidic devices made in thermoplastics PMMA and COP. The aim is to use the approach as an intermediate step between rapid prototyping in PDMS and high-volume production in plastics. An optimized approach will enable rapid testiling of designs and reduce the time and cost of microfluidic chip development. Results showed that epoxy molds can be made consistently and can be applied to hot embossing of thermoplastic materials, which when combined with micromilling can rapidly produce prototyped thermoplastic microfluidic devices at a medium volume production scale.