ORC driven Heat Pumps (HP-ORC) offer a promising technology of thermally driven heat pumps (TDHPs) for domestic applications. Recently, a 40 kW HP-ORC unit based on gas supported turbomachinery has been investigated in which the ORC radial turbine drives the HP centrifugal compressor, offering an oil free and high power density solution. The radial compressor and the radial turbine have tip diameters of the order of 20mm and the system has been tested at rotor speeds in excess of 200 krpm with shaft powers up to 2.4 kW, running with R134a. The compressor and the turbine were operated at pressure ratios of up to 2.8 and 4.4, while reaching thermal COP of the order of 1.5 and isentropic compressor and turbine efficiencies in excess of 70%, thus validating the HP-ORC concept based on small-scale turbomachinery. However, performance limitations were encountered due to suboptimal heat exchanger, working fluid and turbomachinery design. This article presents a full thermo-economic optimization of the HP-ORC enabling the identification of the best trade-off Investment Cost/ COP. Several working fluids have then been compared, revealing that a compromise is to be found between best cost/efficiency trade-off, highest performances achievable and technical feasibility. It also showed a thermal COP improvement potential up to 30% compared to the existing experimental system. Finally, the thermo-economic results of the HP-ORC have been compared with other typical TDHPs, such as absorption heat pump.