The United States Department of Energy (DOE) has identified three means to transport and delivery hydrogen at large scale [1]. Each of the approaches requires the presence of high pressure hydrogen systems. Currently DOE set its fueling station pressure targets at approximately 875 bar with flow rates up to 100 kg/h [1]. Among the other targets for hydrogen compression systems, DOE identified the uninstalled cost target for the FY 2020 at 275,000 $, the energy requirement at 1.6 kWh/kg, availability equal to 85% and annual maintenance cost equal to 4% of the uninstalled cost[1] [1]. The current mechanical compressors cannot achieve the DOE targets and they have several additional drawbacks working at the specified operating conditions. Valid alternative processes are represented by electrochemical compression (EC) systems and thermal compression systems, exploiting the properties of suitable hydrogen absorption materials. Here, an alternative two-stage hybrid compressor system is proposed, with a first stage (lower pressure) EC, coupled in series with a second stage (higher pressure) metal hydride (MH) thermal compression system. The EC operates at compression ratios on the order of 10-20, reaching pressures of about 100-200 bar. Molecular hydrogen is oxidized at the anode producing protons and electrons. They are driven through the proton exchange membrane and combine with electrons at the cathode to deliver high pressure hydrogen. The outlet pressure is maintained at relatively low values (≤ 100-200 bar) in order to avoid hydrogen back diffusion. The second stage of the system, operating at higher pressures, is comprised of a thermal compression system, based on MH materials. Such compounds absorb hydrogen in an exothermic chemical reaction and release the absorbed hydrogen in the reverse endothermic chemical reaction. Their equilibrium pressure is a direct exponential function of the operating temperature, determined by the Van’t Hoff equation. Therefore, providing high temperature thermal power during the desorption process, the hydrogen pressure can be increased without the use of electricity. The paper presents the results obtained from two combined projects, funded by DOE, involving Greenway Energy, Savannah River National Laboratory, University of South Carolina, NIST and Sustainable Innovation. A techno-economic high level model of the hybrid system has been developed in order to assess the performance of the system under different operating conditions and to evaluate the existing gap with the DOE techno-economic targets. Several MH materials have been examined, including rare earth based materials (such as LaNi5, MmNi5, etc) and Ti based MHs. The objective of the analysis was the minimization of: (1) operating temperature, (2) material cost and (3) required thermal power (i.e. material reaction enthalpy minimization). Three main existing material formulations, based on Ti compounds, have been downselected as the candidate materials having the best potential for the current application. The selected materials can reach equilibrium pressures on the order of 900 bar at temperatures on the order of 100-150 °C. Several MEA concepts have been examined for the EC, to find the optimized solution to be coupled with the MH system. Mainly the performance of systems comprised of more traditional PFSA membranes (such as Nafion® membranes) was compared with the one of more innovative polybenzimidazole (PBI) membranes. The latter membranes have shown long term stability, carrying out selected experimental tests. They also showed several other advantages over Nafion® membranes, especially in terms of integrated system performance. EC systems equipped with PBI membranes operating at about 170 °C and at current density of about 2.5 A/cm2 can provide the required thermal power to drive the MH system, recovering the waste power available from the EC system. This results in high energetic and exergetic efficiencies with no need for external thermal power. The hybrid system can closely approach the DOE targets even with the currently available systems, equipped with PBI membranes. The main existing gaps between the targets and the current performance have been identified and analyzed. Specific analyses have been carried out for the MH system, demonstrating that a material with reaction enthalpy on the order of 22 kJ/molH2 and raw material cost of about 1.5 $/kg can meet the targets. A high-throughput genome based technique has been developed and validated, including material synthesis, characterization and numerical modeling prediction. The technique is used and applied to develop new low reaction enthalpy and, especially, low cost MH materials for hydrogen compression systems.