Emerging environmental threats such as novel chemical compounds, biological agents, and nanomaterials present serious challenges to traditional models of risk analysis and regulatory risk management processes. Even a massive expansion of risk and life-cycle assessment research efforts is unlikely to keep pace with rapid technological change resulting in new and modified materials with changing properties. Therefore, it is essential to have a framework for interpreting available information in the context of high uncertainty and a strategy for prioritizing research efforts to reduce those uncertainties that are most critical. We discuss how integrating the three analytic approaches of risk assessment, life-cycle assessment, and multicriteria decision analysis into a framework permits understanding uncertainty and prioritizes needs for scientific research. Our approach is illustrated with two separate cases: nanomaterials and contaminated sediment remediation.