The influence of the regional 3-D geology on the synthetic earthquake ground motion prediction is herein assessed, studying the seismic response of Kashiwazaki-Kariwa nuclear power plant (KKNPP), during the 2007 Niigata seismic sequence (west Japan), so to explore the potentiality and practicability of the innovative computational tools available. This applicative case study was chosen within the framework of the SINAPS@ project, the first French research project which aims to propose a continuous approach from the fault to the structure and equipment's, accounting explicitly for the uncertainties related to the databases and the models. A source-to-site numerical model of the region (≈ 60 km wide) is built-up and calibrated for small aftershocks including surface topography, Japan sea and complex 3-D underground foldings. The impact of complex 3-D geology in terms of seismic response at KKNPP is quantified, by comparison with the simplified transverse isotropic geology. This validation stresses the importance of the 3-D geology and explicates the observed high ground motion spatial variability, as well as the strong dependence of the site response on the incident wave obliquity. The synthetic wave-field (0-5 Hz) is obtained by employing SEM3D, a high-scalable software tailored based on the Spectral Element Method. This high-fidelity code performs efficiently (thanks to its high scalability on parallel supercomputers) when refining the model spatial discretization and increasing the bedrock-to-sediment shear wave velocity gradient. The synthetic wave-motion simulated was exploited as input motion for a Soil-Structure Interaction numerical model (Finite Element Method-Boundary Element Method, Code_Aster-MISS3D) of the standard reactor building at KKNPP. The impact of the 3-D geology is assessed therefore on the structural components, highlighting a considerable amplification compared to the case of layered one.