The pursuit of sustainability has catalyzed broad investment in the research, development, and deployment (RD&D) of innovative water, sanitation, and resource recovery technologies, yet the lack of transparent and agile methodologies to navigate the expansive landscape of technology development pathways remains a critical challenge. This challenge is further complicated by the higher levels of uncertainty that are intrinsic to early-stage technologies. In this work, we review and synthesize published literature on the sustainability analyses of water and related technologies to present Quantitative Sustainable Design (QSD) – a methodology to expedite and support technology RD&D. With a shared lexicon and a structured approach, QSD facilitates interdisciplinary communication and research consistency. In introducing QSD, we review existing studies to highlight best practices and discuss them in the context of the specific steps of QSD, which include defining the problem space, establishing simulation algorithms, and characterizing system sustainability across economic, environmental, human health, and social dimensions. Next, we summarize tools for QSD execution and provide recommendations to account for uncertainty in this process. We further discuss applications of QSD in the fields of water/wastewater and beyond (e.g., renewable fuels, circular economy) in combination with uncertainty, sensitivity, and scenario analyses to generate the desired types of insight. Finally, we identify future research needs for sustainability analyses to advance technology RD&D. Ultimately, QSD can be used to elucidate the complex and intertwined connections among design decisions, technology characteristics, contextual factors, and sustainability indicators, thereby supporting transparent, consistent, and agile RD&D.