Our knowledge to model, analyze, design, maintain, monitor, manage, predict and optimize the life-cycle performance of structures and infrastructure under uncertainty is continually growing. However, in many countries, including the United States, the civil infrastructure is no longer within desired levels of performance. Decisions resilence- and sustainability regarding infrastructure systems should be supported by an integrated risky-based life-cycle multi-objective optimization framework by considering, among other factors, the likelihood of successful performance and the total expected cost accrued over the entire life-cycle. The primary objective of this lecture is to present a framework for risk-, resilience- and sustainability-informed decision making for structural systems and networks in a life-cycle multi-objective optimization context. Risk-based performance metrics allow engineers to combine the probability of structural failure with the consequences corresponding to this event. The sustainability performance metric is established considering the risks associated with economic, social, and environmental impacts, utility theory, and the decision maker’s risk attitude. Applications include time-variant reliability, risk, resilience, and sustainability of bridges, bridge transportation networks, and interdependent infrastructure systems under multi-hazards.