Technical challenges connected to new technology nodes are becoming increasingly complex due to extreme scaling (every atom matter) along 3D geometries and the introduction of new materials. Simulation tools are thus needed to accelerate time-to-development. In this paper, we present a new model for GAA nanosheet transistors accounting for material imperfection (e.g. atomic defects and process residuals) and quantum effects, which allows connecting material properties and process-related atomic scale defects to electrical device performances (Ion, SS) and reliability (BTI, leakage current and SILC, BD and TDDB/VBD, noise). The model is based on a self-consistent solution of Poisson-Schroedinger equations coupled with charge transport, which includes drift and diffusion, hopping, thermo-ionic emission, and Trap- Assisted Tunneling. Ab-initio and process simulations are used to connect defect atomic structure to material and interface properties, key to capture device statistics and reliability. Circuit operations can be also simulated by exploiting mixed mode operation, capturing device sensitivity to real operating conditions, thus connecting test vehicle DC/AC/transient/pulsed regime.