Supercritical-CO2(S-CO2) cycle systems have appeared as an attractive option for waste-heat recovery from internal combustion engines(ICEs) thanks to the advantages offered by CO2as a working fluid, which is nontoxic and non-flammable, and does not suffer decomposition at high temperatures. Since the high density of CO2in the supercritical region enables compact component design, various S-CO2cycle systemconfigurations have been presented involving different layouts and combinations of heat exchangers with which to enhance heat recovery from both engine exhaust gases and jacket waterstreams. Despite the thermodynamicperformance improvement offered by more complex configurations, the additional heat exchangers bring extra costs and therefore key thermo-economic decisions need to be considered carefully during the design and development of suchsystems. This paper seeks to conduct both thermodynamic and economic (cost) assessments of a variety of S-CO2cycle system configurationsin ICE waste-heat recovery applications, with results indicating that in some cases a significant thermodynamic performance improvement can compensate the extra costs associated with a morecomplex system structure. The comparison results across a range ofICEs can also be a valuable guide for the early-stage S-CO2cycle system design in ICE waste-heat recovery andother similar applications.