This paper presents recent advances in response sensitivity, probabilistic response and reliability analyses of structural and geotechnical systems. These developments are integrated into general-purpose nonlinear finite element (FE) software frameworks and provide the structural engineers with analytical and computational tools to propagate uncertainties through advanced large-scale nonlinear simulations and obtain probabilistic estimates of the predicted system response performance. The Direct Differentiation Method (DDM) for accurate and efficient computation of FE response sensitivities is extended and applied to large-scale nonlinear Soil-Foundation-Structure-Interaction (SFSI) systems.