This study examines the role and potential of science, technology, and innovation (STI) as key enablers for catalytic change in the world’s achievement of Sustainable Development Goal 6 (SDG6) on clean water and sanitation for all. It highlights the deep-rooted relationship between the two and analyses how STI can contribute significantly to overcoming the persistent challenges in delivering SDG 6, with a focus on the distribution and delivery of safe water and sanitation, the integrated water resource management, and addressing inequalities in the sector, notably in relation to gender. The study also highlights the potential of frontier technologies. Countries are recommended to consider STI as part of an answer that requires careful context-specific policies to bring it to fruition. They include embracing decentralized solutions and considering nexuses that water shares with other sectors. The report also suggests how the international community can go a long way to assist countries in achieving SDG 6, notably by pooling its knowledge and technological know-how through sharing mechanisms and by developing innovative financial mechanisms to support water and sanitation projects in developing countries.