This study explores the uptake and potential application of nature-based solutions (NbS) that are particularly promising for small-scale farmers, ranchers, and food entrepreneurs operating in arid and semi-arid regions. Studying the adoption of NbS by local food entrepreneurs (LFEs), including related strengths and limitations, remains an area of exploration due to their potential to optimize interventions that foster environmental sustainability at the intersection of people, animals, and natural ecosystems (i.e., One Health). A multi-method design was used, including literature review, questionnaires, and semi-structured key informant interviews to assess adaptation needs and NbS among a sample of LFEs located in Southern AZ, USA. The findings revealed that existing NbS have been introduced mostly through learning-by-doing practices that are bounded by economic and technological resource constraints. The paper describes a range of accessible approaches and practices that can be piloted and/or scaled up to enhance local food system resilience and contribute to the overlapping health of people, animals, and natural ecosystems. The priority adaptation pathways for NbS were identified to be funding and financing and the co-creation and sharing of knowledge through peer-to-peer and expert-to-peer approaches. The results suggested that AZ LFEs are likely to adopt NbS based on their capacity to address priority climate-driven issues, revenue generation potential, and seamless augmentation with existing food production and operational activities.