Istanbul is a mega city with various coastal utilities located on the northern coast of the Sea of Marmara. At Yenikapi, there are critical vulnerable coastal utilities, structures, and active metropolitan life. Fishery ports, commercial ports, small craft harbors, passenger terminals of intercity maritime transportation, waterfront commercial and/or recreational structures with residential/commercial areas and public utility areas are some examples of coastal utilization that are vulnerable to marine disasters. Therefore, the tsunami risk in the Yenikapi region is an important issue for Istanbul. In this study, a new methodology for tsunami vulnerability assessment for areas susceptible to tsunami is proposed, in which the Yenikapi region is chosen as a case study. Available datasets from the Istanbul Metropolitan Municipality and Turkish Navy are used as inputs for high-resolution GIS-based multi-criteria decision analysis (MCDA) evaluation of tsunami risk in Yenikapi. Bathymetry and topography database is used for high-resolution tsunami numerical modeling where the tsunami hazard, in terms of coastal inundation, is deterministically computed using the NAMI DANCE numerical code, considering earthquake worst case scenarios. In order to define the tsunami human vulnerability of the region, two different aspects, vulnerability at location and evacuation resilience maps were created using the analytical hierarchical process (AHP) method of MCDA. A vulnerability at location map is composed of metropolitan use, geology, elevation, and distance from shoreline layers, whereas an evacuation resilience map is formed by slope, distance within flat areas, distance to buildings, and distance to road networks layers. The tsunami risk map is then computed by the proposed new relationship which uses flow depth maps, vulnerability at location maps, and evacuation resilience maps.