Rapid changes in the social and economic environment in which agriculture is developing, together with the deterioration of the natural resource base threatens sustainability of farm systems in many areas of the world. For vegetable farms in South Uruguay, survival in the long term depends upon the development of production systems able to reduce soil erosion, maintain or improve physical and biological soil fertility, and increase farmer’s income to socially acceptable levels. We propose a model-based explorative land use study to support the re-orientation of vegetable production systems in South Uruguay. In this paper we present a new method to quantitatively integrate agricultural, environmental and socio-economic aspects of agricultural land use based on explicit design objectives. We describe the method followed to design and evaluate a wide variety of land use activities for Canelón Grande (South Uruguay) and we illustrate the usefulness of this approach in an ex-ante evaluation of new farming systems using data from 25 farms in this region. Land use activities resulted from systematic combination of crops and inter-crop activities into crop rotations, different crop management techniques (i.e., mechanisation, irrigation and crop protection) and animal production. We identified and quantified all possible rotations and estimated inputs and outputs at crop rotation scale, explicitly considering interactions among crops. Relevant inputs and outputs (i.e., soil erosion, balance of soil organic matter and nutrients, environmental impact of pesticides, labour and machinery requirements, and economic performance) of each land use activity were quantified using different quantitative methods and following the target-oriented approach. By applying the methodology presented in this paper we were able to design and evaluate 336,128 land use activities suitable for the different soil types in Canelón Grande and for farms with different availability of resources, i.e., land, labour, soil quality, capital and water for irrigation. After theoretical evaluation, a large subset of these land use activities showed promise for reducing soil erosion, maintaining soil organic matter content of the soil and increasing farmer’s income, allowing improvement of current farming systems in the region and providing a widely diverse set of strategic options for farmers in the region to choose from. This method can be used as a stand-alone tool to explore options at the field and farm scale or to generate input for optimisation models to explore options at the farm or regional scale.