Worldwide energy demand is projected to increase 40% by 2035. Thermoelectric power generators could be a rapid, powerful way to meet the increased need for energy by converting wasted heat energy into useful electrical energy. However, inter-disciplinary factors determining the feasibility of widespread thermoelectric power generation systems have been minimally explored. This work connects materials and manufacturing costs, materials properties, and system level design to identify the factors necessary for successful thermoelectric generators. First, an economic analysis links materials and manufacturing costs with material performance to produce a thermoelectric device cost-performance metric. Current and potential thermoelectric materials are evaluated using this metric to determine which materials are promising candidates. Next, thermoelectric energy system modeling demonstrates the potential for increased energy efficiency in existing energy systems. Thermoelectric waste heat recovery is simulated for three applications: a home water heater, an automotive exhaust system, and an industrial furnace. The impact of system and material parameters on power generation efficiency is determined. Engineering at the nanoscale produces materials with combinations of properties absent in the natural world, enabling tunable and enhanced energy conversion in these systems. In particular, zinc oxide nanowires may offer improved thermoelectric energy conversion. Finally, characterization of electrothermal transport phenomena in single zinc oxide nanowire structures demonstrates the impact of nanowire contacts on the realization of functional nanowire materials.