This study attempts to present an urban road transportation strategy focusing on the mitigation of both GHGs emission and public health damage, taking Xiamen City as a case study. We developed a Public Health and GHGs Emission model to estimate the impacts of direct energy-consumption-related GHGs emissions and public health damage in Xiamen’s road transportation strategies from 2008 to 2025, considering the environmental benefits and economic costs. Two scenarios were designed to describe future transportation strategies for Xiamen City, and mitigation potentials for both GHGs emission and public health costs were estimated from 2008 to 2025 under a series of options. The results show that enacting controls on private vehicles would be most effective to GHGs mitigation, while enacting controls on government and rental vehicles would contribute the most to NO2 and PM2.5 reductions. Compared with the Business as Usual scenario, the Integrated scenario would achieve about a 68% energy consumption reduction and save 0.23 billion yuan (95% CI: 0.16, 0.32) in health costs in 2025. It is clear that integrated and advisable strategies need to mitigate the adverse impacts of urban road vehicles on GHGs emissions and public health and economic costs, particularly in regions of rapid urbanization.