This study presents an economy-wide analysis of Japan’s pathways to achieve net-zero CO2 emissions by 2050 using the Japan-REGEN integrated energy-economy model. A suite of scenarios evaluates the impacts of policy targets, technology costs, fuel imports, and resource constraints, including reference, intermediate decarbonization, and net-zero pathways with key sensitivities. Results show that electrification and rapid expansion of renewable energy are central to deep decarbonization, with electricity demand rising significantly and renewables supporting a large share of generation by mid-century. Low-carbon fuels such as hydrogen, renewable natural gas, and synthetic fuels play critical roles in hard-to-abate sectors, while CO2 removal strategies are required to offset residual emissions. Scenarios highlight the importance of key technology and other sensitivities in shaping outcomes. Achieving net-zero will require coordinated infrastructure development and a flexible, multi-path strategy.