Global demand for agricultural products continues to grow. However, efforts to boost productivity exacerbate existing pressures on nature, both on farms and in the wider landscape. There is widespread appreciation of the critical need to achieve balance between biodiversity and human well-being in rural tropical crop production landscapes, that are essential for livelihoods and food security. There is limited empirical evidence of the interrelationships between natural capital, the benefits and costs of nature and its management, and food security in agricultural landscapes. Agroforestry practices are frequently framed as win-win solutions to reconcile the provision of ecosystem services important to farmers (i.e., maintaining soil quality, supporting pollinator, and pest control species) with nature conservation. Yet, underlying trade-offs (including ecosystem disservices linked to pest species or human-wildlife conflicts) and synergies (e.g., impact of ecosystem service provision on human well-being) are seldom analysed together at the landscape scale. Here, we propose a systems model framework to analyse the complex pathways, with which natural capital on and around farms interacts with human well-being, in a spatially explicit manner. To illustrate the potential application of the framework, we apply it to a biodiversity and well-being priority landscape in the Southern Agricultural Growth Corridor of Tanzania, a public-private partnership for increasing production of cash and food crops. Our framework integrates three main dimensions: biodiversity (using tree cover and wildlife as key indicators), food security through crop yield and crop health, and climate change adaptation through microclimate buffering of trees. The system model can be applied to analyse forest-agricultural landscapes as socio-ecological systems that retain the capacity to adapt in the face of change in ways that continue to support human well-being. It is based on metrics and pathways that can be quantified and parameterised, providing a tool for monitoring multiple outcomes from management of forest-agricultural landscapes. This bottom-up approach shifts emphasis from global prioritisation and optimisation modelling frameworks, based on biophysical properties, to local socio-economic contexts relevant in biodiversity-food production interactions across large parts of the rural tropics.