The 2011 Tohoku Earthquake Tsunami exposed the heightened vulnerability of elderly and physically disabled individuals in coastal regions. In response, Japan has begun to partially permit car evacuation during significant tsunami events. However, since road congestion may increase overall mortality, developing effective evacuation plans that account for car use remains a critical challenge. While previous research has indicated that the influence of vehicle use on the effectiveness of newly established tsunami evacuation shelters depends on regional characteristics, comprehensive analyses covering multiple regions are still limited. This study aims to advance understanding of this issue through a comparative simulation analysis of two coastal areas—Owase City and Kiho Town in Mie Prefecture, Japan—using a multi-agent tsunami evacuation simulation model. The simulations, based on the Nankai–Tonankai Earthquake Tsunami scenario, evaluate mortality under two conditions: one considering only pedestrian evacuees and another with a mixed mode including car evacuees. Results revealed that incorporating car evacuation reduced mortality rates under the existing shelter distributions in both regions. However, in scenarios introducing a new shelter, a greater number of locations led to reduced mortality in the pedestrian-only scenario than in the mixed-mode scenario. These findings underscore the importance of considering regional characteristics when planning shelter placements and indicate that the inclusion of car evacuation substantially alters optimal shelter strategies.