According to the World Health Organization, 785 million people lack access to basic drinking water facilities. Point-of-use (POU) water disinfection technologies can be adopted to help address these issues by treating water at the household level; however, navigating various POU technologies can be difficult. While numerous conventional POU devices exist (e.g., boiling water, chlorination), emerging technologies using novel materials or advanced processes (e.g., membranes, ultraviolet) have been developed and claim to be lower cost with higher treatment capacity. However, it is unclear if these claims are substantiated and how technologies compare in terms of cost and environmental impacts while achieving a necessary level of disinfection. This research uses quantitative sustainable design methods to assess four different POU technologies (chlorination using sodium hypochlorite, silver nanoparticle-enabled ceramic water filter, ultraviolet mercury lamps, and ultraviolet light-emitting diodes). Leveraging open-source Python packages (QSDsan), cost (in USD∙cap-1∙yr-1) and global warming potential (in kg CO2 eq∙cap-1∙yr-1) of these technologies were assessed using techno-economic analysis and life cycle assessment. We set raw water types to be characteristic surface and ground waters to capture their impacts on technology sustainability, and we performed uncertainty and sensitivity analyses to reveal the drivers. We further included contextual analysis across the world with location-specific data (e.g., raw water type and properties) to inform the choice of appropriate technology in a given community. Results of this study can potentially provide valuable insights for decision-makers, non-profit organizations, and future researchers in developing sustainable approaches for ensuring access to safe drinking water through POU technologies.