South East Asia's agricultural landscape is rapidly transitioning from subsistence to intensive and market-oriented production, often with negative impacts on soil fertility. Ensuring that this transition is conducted in a sustainable way is critical, especially for the poorest who rely exclusively on natural resources that are of limited quality and quantity. This study aims to evaluate sustainable intensification options for smallholder ethnic minority farmers of the Lao uplands. Following a systematic selection of case study crop-livestock farms with different degrees of diversification and market orientation, we adopted a detailed nutrient flow approach to quantify nitrogen (N) and phosphorus (P) balances at farm level using a whole farm modelling tool. This was then used to simulate alternative sustainable intensification options relative to the baseline and their impact on farm performance and N and P cycling. Irrespective of the intensification level, nutrient balances were negative on all farms, with net nutrient removal between −34 and −130 kg N ha−1y−1 and between −9 and −20 kg P ha−1y−1. The positive effect of the sustainable intensification options on selected system performance variables was up to 15 times higher when its baseline value was low, i.e. when potential for improvement was high. Compared to the baseline (rice and maize monocropping systems), fallow plots during the dry season and low level of residues recycling, all intensification options increased land productivity and N balance by at least 12% on each farm, whereas the P balances were negatively impacted. The positive effects on the N balances might not be sufficient to reverse nutrient depletion, and additional nutrient inputs would be necessary. Four management principles are key to ensure a smooth transition from subsistence to intensive production: no residue burning, stay diverse, integrate livestock and use small amounts of P mineral fertilizer. If combined with efficient and integrative agricultural extension, seed systems and market development, these basic principles could be the key success factor for a sustainable development of the Lao uplands.