Changing global economic conditions and efforts to reduce greenhouse gas emissions to reduce their impact on climate and public health is driving the need to develop alternative technologies to meet the demands of heavy-duty vehicles and increase propulsion system efficiency. This study combines a Hydrogen internal combustion engine (H2-ICE) for its near zero CO2 emissions capability, with electrically assisted turbocharging, exhaust energy recovery, and mild hybridization to maximize propulsion system efficiency in real-world driving. The focus is on model-based integration and optimization of a technology package termed as the Integrated, Turbogeneration, Electrification, and Supercharging (ITES) system to demonstrate its potential for low emissions, high efficiency, and reduced cost will be demonstrated. In a previous study, a H2-ICE and aftertreatment concept for a MY2027 7.7L medium heavy-duty on-road engine was developed and evaluated through 1D simulation. The concept was to convert a diesel engine by changing the cylinder head to implement a PFI lean H2 SI combustion system with two-stage turbocharging and no external EGR. The concept was optimized for compression ratio, valve lift profiles, turbocharging, aftertreatment size/specification, and calibration using 1D system simulation in GT-SUITE. In this study, the H2-ICE concept performance was further improved by integrating the ITES system and evaluated through 1D simulation. The ITES system replaces the conventional low-pressure stage of the boosting system and adds the capability of electrically assisted turbocharging, turbogeneration from exhaust energy, and P1 mild-hybridization. Applying a model-based approach, the H2-ICE & ITES component sizes were optimized for the best performance and emissions benefit. Using 1D simulation of validated models, the efficiency benefit of the ITES system on engine and vehicle level system was predicted. Finally, a vehicle level fuel consumption comparison was made between H2-ICE concept, H2-ICE+ITES concept and a fuel cell electric powertrain for Class 6-7 medium heavy duty truck application.