In this paper we will present integrated time dependent variability tool flow that links statistical TCAD simulations, statistical compact model extraction and statistical circuit simulation. This allows the concepts of Design-Technology Co-Optimization (DTCO) to be extended into the reliability domain. The simulations are based on Gold Standard Simulations' (GSS) 3-D Kinetic Monte Carlo TCAD technology, which enables the simulation and analysis of the trapping/de-trapping history of large ensembles of microscopically different transistors. The results of the physical simulation are than captured in accurate time dependent statistical compact models. As a result, accurate statistical circuit simulation can trace the statistical impact of the degradation on the functionality of the underlying circuits and systems.