This study investigated cost‐effective energy strategies for realizing net zero CO2 emissions in Japan by 2050, employing an energy system optimization model with hourly electricity balances. The detailed temporal resolution enables the model to capture the intermittency of variable renewable energy (VRE) and the costs of system integration measures. Siting constraints on VRE, such as prohibiting solar PV and onshore wind developments in forests and offshore wind developments inside fishery rights areas, are incorporated in the model to reflect the environmental protection and social acceptance perspectives. Simulation results imply that a well‐balanced power generation mix, combining renewables, nuclear, gas‐fired with carbon capture and storage, as well as ammonia‐fired, would contribute to curbing mitigation costs. In contrast, a simulation case with very high VRE penetration poses economic challenges. The average shadow price of electricity in 2050 in a 100% renewables case (RE100) is projected to be more than doubled from a reference case which is based on middle‐of‐the‐road assumptions. Marginal CO2 abatement cost in 2050 increases from 49,200 JPY/tCO2 in the reference case to 75,300 JPY/tCO2 in the RE100 case. The economic viability of high VRE penetration is improved by relaxing the siting constraints, although it may raise environmental and social concerns.