The goal of this study is to comparably assess the relative sustainability of several readily available POU disinfection technologies. Specifically, the objectives of this work are to (i) characterize the overall cost and environmental impacts while considering necessary disinfection efficacy of these technologies and (ii) elucidate drivers for sustainability to better inform appropriate adoption in specific contexts. The technologies assessed in this study include: POU chlorination, silver nanoparticle enabled ceramic water filter (AgNP CWF), UV with mercury lamp, and UV with light-emitting diode (LED). This study leverages the quantitative sustainable design (QSD) methodology for TEA, LCA, and disinfection efficacy assessment using an open-source Python packages QSDsan (QSD for sanitation and resource recovery systems). Uncertainty was incorporated in the assumptions inputted into the models, and sensitivity analysis (via Spearman's rank correlation coefficients) was completed to identify key drivers of sustainability. The impact of water quality was evaluated by updating assumptions considering two different water compositions (surface and groundwater), and a technology adoption period ranging from 1 to 15 years was assessed. A contextual analysis was also included to reflect the implications of location-specific parameters on technology deployment in ten different communities across the world. Findings of this study are expected to offer valuable insights for decision-makers, non-profit organizations, and future research endeavors focusing on sustainable approaches to safe drinking water through POU technologies.