It is generally acknowledged that using CO2-based binary mixtures as working fluids in supercritical recompression Brayton cycle for waste heat recovery is a promising technique. This study examines the performance of CO2-Kr (0.76/0.24) and CO2-Xe (0.56/0.44) mixtures, comparing them with pure CO2. Both thermodynamic and thermo-economic considerations are taken into account to establish optimal parameter settings. The findings suggest that the minimum system temperature should be around but not below the critical temperature of the working fluid. The system performs badly at lower pressures and shows nearly the same at higher pressures, with 25 MPa being the recommended value for the main compressor. When the system split ratio and the low temperature recuperator temperature difference are well matched, the heat exchangers exhibit an optimal temperature distribution. The exergy loss distributions of the exchangers in the CO2-Kr and CO2-Xe systems are likewise rather uniform when the input pressure of the main compressor is above the critical pressure of the fluid, typically between 0.2 MPa and 0.4 MPa, enhancing system efficiency. The corresponding temperature difference of the LTR should be within 5 °C above or below the critical temperature of the fluid. This advantageous feature is not immediately apparent in the pure SCO2 cycle.