The twenty-first century is witnessing an explosion in global population, environmental changes, agricultural land disintegration, hunger, and geopolitical instabilities. It is difficult to manage these conditions or standardize improvement systems without thinking of the three main elements or subsystems that are necessary for any meaningful development—namely water (W), energy (E), and food (F). These key elements form what is globally agreed upon as the “WEF Nexus.” While considering them, one should think about the other key factors that influence WEF Nexus, including population’s growth, impacts of environmental changes (including climate change), moderation and adaptation regimes to climate change and climate resilience, loss of biodiversity, and sustainable nature. Together, the WEF Nexus subsystems represent a framework to ensure environmental protection that should be seen as an ethical and socioeconomic obligation. Issues, such as protection of water resources, and strategies and management tools or mechanisms for the use of water assets and agricultural innovations under the obligations of sustainable use, are investigated in this paper. Attention is paid to the relationship between water and food (WF Nexus) or water for food security in various world regions, including the Gulf Cooperation Council (GCC) countries, Central Asia countries and the Caucasus, China, Africa, and Canada. This paper also presents analyses of a great number of up-to-date publications regarding the “Nexus” perspective and its applications and limitations. This paper suggests that the Nexus’ approach, in its different concepts (WEF, WE, WF and EF), can promote sustainable development and improve the quality of life of communities, while preserving natural, human, and social capital, addressing sustainability challenges, and protecting natural resources and the environment for long-term use.