Simulation models of multi-sector systems are increasingly used to understand societal resilience to climate and economic shocks and change. However, multi-sector systems are also subject to numerous uncertainties that prevent the direct application of simulation models for prediction and planning, particularly when extrapolating past behavior to a nonstationary future. Uncertainty analysis for multi-sector systems is further complicated by the fundamentally transdisciplinary nature of multi-sector dynamics research, which can inhibit consistent communications of how uncertainties were treated and the resulting implications for the conclusions of the analysis. This presentation reviews these challenges, provides a common framework for classifying relevant uncertainties, and identifies key research opportunities.