The field of engineered nanomaterial (ENM) risk analysis has matured significantly in the past decade. While there is a suite of new, emerging tools to evaluate ENM risks and make decisions regarding these risks, there has not yet been thorough testing of these tools. This analysis applies and tests three risk screening tools (NanoRiskCat, LICARA nanoSCAN, NanoGRID) using a common case study focused on ENMs designed for water treatment technologies, compares results generated, and highlights key lessons learned and best practices for stakeholders involved in developing and/or applying ENM risk screening tools. NanoRiskCat was found to be most useful for providing a visual aid to characterize the potential exposure and health impact profiles of the ENMs, while LICARA nanoSCAN was most useful for providing guidance on proceeding with ENM-enabled innovations. NanoGRID was helpful for characterizing data on potential ENM exposure and hazards and providing detailed guidance for subsequent laboratory-based testing. At the same time, several key challenges were identified during tool application and testing phases, ranging from minor inconveniences to more complex, foundational issues. Key lessons learned and potential best practices gleaned from this analysis include: i) risk screening tools can be used together in a complementary manner; ii) risk managers and other users should be clear on the selection of underlying data and impacts on results; iii) multidisciplinary teams are essential for tool completion; and iv) continued testing and validation of emerging risk analysis tools for ENMs is a continued research need.