This review is concerned with the leading methods of bottom-up material preparation for thermal-to-electrical energy interconversion. The advantages, capabilities, and challenges from a material synthesis perspective are surveyed and the methods are discussed with respect to their potential for improvement (or possibly deterioration) of application-relevant transport properties. Solution chemistry-based synthesis approaches are re-assessed from the perspective of thermoelectric applications based on reported procedures for nanowire, quantum dot, mesoporous, hydro/solvothermal, and microwave-assisted syntheses as these techniques can effectively be exploited for industrial mass production. In terms of energy conversion efficiency, the benefit of self-assembly can occur from three paths: suppressing thermal conductivity, increasing thermopower, and boosting electrical conductivity. An ideal thermoelectric material gains from all three improvements simultaneously. Most bottom-up materials have been shown to exhibit very low values of thermal conductivity compared to their top-down (solid-state) counterparts, although the main challenge lies in improving their poor electrical properties. Recent developments in the field discussed in this review reveal that the traditional view of bottom-up thermoelectrics as inferior materials suffering from poor performance is not appropriate. Thermopower enhancement due to size and energy filtering effects, electrical conductivity enhancement, and thermal conductivity reduction mechanisms inherent in bottom-up nanoscale self-assembly syntheses are indicative of the impact that these techniques will play in future thermoelectric applications.