The 2030 goal for the implementation of the Sustainable Development Goals (SDGs) gives rise to challenging questions stemming from the inherent interconnections and potential competition between primary resources. ‘Economic Growth’ and ‘Clean Water and Sanitation’ are intimately related SDGs. Access to quality water is critical to growth, but as economies and populations grow, so does their demand for water. As pressures on water systems increase, existing and proposed economic activities are subject to growing water related stresses, such as service disruptions, droughts, floods, and contamination. Growth is dependent upon investment in critical resources to mitigate water related risks and for sustainable water allocation. Highly interdependent water, energy, and food systems are reflected in SDGs, raising questions about how to achieve the security goal for water without sacrificing that for food; and giving rise to questions of how to quantify the interconnections and assess the possible trade-offs for sustainable pathways into the future. This commentary addresses these complex and critical challenges to achieving the interconnected goals at different scales and in light of scarce or incompatible data, and the many stakeholders involved. It offers thoughts on holistic approaches to complement the SDGs and facilitate science-based decision making, monitoring, assessment and cooperation. The paper reflects on World Water Week 2016, reviews global risks and societies’ perceptions of those risks. Defining ‘resource nexus’, the paper shares examples that illustrate the concept and calls for efforts to reduce inter-dependencies and increase synergies between the primary resources through technology, policy, and adaptations to human consumption and conservation behaviors. The paradigm shift proposed, while critically needed, is not possible without the resource nexus platform.