Supercritical CO2 (sCO2) is taking a growing interest in both industry and academic communities as a promising technology capable of high efficiency, flexibility, and competitive capital costs. Many possible applications are studied in the energy field, from nuclear power plants to concentrating solar power and waste heat recovery (WHR). To evaluate the competitiveness of sCO2 cycles relative to other competing technologies, mainly steam and organic fluid Rankine cycles (ORC), a specific techno-economic analysis is needed to fairly compare the different technologies for each application, in order to find the most appropriate market position of the innovative sCO2 plants, compared to the existing steam and ORC solutions. In the present study, techno-economic analysis and optimization have been conducted focusing on WHR applications, for different sizes and cycle parameters operating conditions using an in-house simulation tool. The analyzed cycles were first optimized by aiming at maximizing the net electrical power and then aiming at minimizing the specific capital cost. As a result, compared to traditional plants, we obtained that in the first case, the more complex sCO2 cycle configuration shows competitive performance, while in the second case, the simpler sCO2 cycle configuration has a lower specific cost for the same electrical power produced (with a difference of approximately −130 €/kW compared to the steam cycle). In general, while traditional technologies confirmed a good tradeoff between performance and cost, supercritical CO2 cycles show attractive characteristics for applications requiring simplicity and compactness, guaranteeing in the meantime other technical advantages such as water-free operation.