The impacts of anthropogenic and non-anthropogenic threats on water resources have increased in many regions worldwide. Moreover, studies identify that these impacts can be more significant in the future, increasing human and ecosystem threats. As a result, policymakers and local stakeholders have implemented solutions to mitigate the impact of the threats in terms of water quantity and quality. This study proposes an effective response analysis framework to measure the effectiveness of local responses considering the current and future water security threats. In addition, the research intends to identify the impact of climate change, water demand modification and land use and land cover change in the water security threats in 2040 and how this effect could impact the local farmers in an agricultural frontier in Brazil. The study results demonstrate a trend of future threats to water security in grid cells with more economic vulnerability in the region analysed. The effectiveness assessment shows that 70% of the farmers in more vulnerable areas have indicated the higher effectiveness of soil, land and water management strategies related to water security issues. Finally, the results of the stakeholder consultation reveal a higher potential to implement green infrastructure in mitigating water security threats.