Nature-based solutions (NBSs), defined as actions that work with and enhance nature, providing environmental, social, and economic benefits, play a pivotal role in accomplishing multiple objectives within the Water–Ecosystem–Food Nexus domain. They contribute to facilitating the transition to more resilient agrifood systems and providing an evidence base for a broader Nexus policy dialogue. This paper describes the stepwise methodology developed in the EU-funded LENSES project to carry out a comprehensive analysis of NBSs in six pilot areas in five Mediterranean countries and presents the results of NBS implementation in four pilot areas, highlighting obstacles and opportunities. The methodology includes the development of an analytical evaluation framework and a comprehensive catalogue of Nexus-related NBSs, whose suitability needs to be assessed at the local level to achieve better use of protected/natural ecosystems, increase the sustainability and multifunctionality of managed ecosystems, and design and manage novel ecosystems. Subsequently, in a collective learning process that supported the operationalisation of the WEF Nexus, NBSs were identified that address specific contextual vulnerabilities, improve water distribution, and enhance food security while preserving ecosystems and supporting adaptation to climate change. The added value of the proposed methodology lies in the multi-stakeholder participatory approach to gain in-depth knowledge of local agri-food systems, including their main WEF-related challenges, and to facilitate overcoming barriers to NBS implementation. Finally, a final survey was conducted among a small group of purposively selected stakeholders to gain some insight into their perceptions of the impact of NBS and to gather some opinions on the main barriers and opportunities.