Water, energy, and food security are essential for maintenance and human survival. This research applied an approach for the water–energy–food system to a watershed in the Atlantic Rainforest in Southern Brazil. It is based on a WEAP system that was developed and evaluated future water demand scenarios for the 2020–2050 timespan. The Sustainability Index (SI) was used to assess the scenarios to propose an alternative to compare the current development trend. The results indicated that by 2050, the necessary flow for different water uses would be 78.75% greater than in 2020 while maintaining the present scenario (C_REF). Substituting part of the hydroelectric energy by photovoltaic solar energy (C_EAL), implementing watershed action masterplans as a water resource instrument (C_GES), and integrating these scenarios (C_INT) will reduce the current demand ranging from 8.96% to 24.59%. The average flow would decrease by 28.44% and 29.07%, respectively, by evaluating water availability in climatic change scenarios (C_MCL) for the RCP 4.5 and 8.5 scenarios. Compared with the reference scenario C_REF, C_INT presented an improved SI (0.1231), while C_MCL 8.5 presented the worse (−0.0047). Therefore, resources must be generated holistically so that one segment does not negatively impact the others. The findings highlight the pressing need for Santa Catarina State to implement effective management strategies targeting specific sectors, particularly the industrial and human consumption supply sectors. It is imperative to propose adaptation plans and implement actions that foster the reduction in water demands while also providing subsidies and guidance to the industrial sector on responsible water usage to prevent any negative impact on their productivity in the future. Comprehensive plans and policies should be formulated to ensure integration and coherence among various sectors involved in water resource management.