In spite of the very large hydropower potential given from the melting snow and ice of Himalayas, Nepal’s population has little hydropower production. The high use of fossil fuels and biomasses results in measurable air pollution, even in the mountain areas. Hydropower planning and implementation, in the face of the changing climate, is therefore paramount important. We focus here on Nepal, and particularly on the Dudh Koshi river basin, with a population of ca. 170,000 people, within an area with large potential for hydropower production. Our main objectives are to (i) preliminarily design a local hydropower grid based on a distributed run of river ROR scheme, and (ii) verify the resilience of the grid against modified hydrology under perspective climate change, until the end of the century. To do so, we set up and tune the Poli-Hydro semi-distributed glacio-hydrological model, mimicking the complex hydrology of the area. We then modify a state of the art algorithm to develop and exploit a heuristic, resource-demand based model, called Poli-ROR. We use Poli-ROR to assess the (optimal) distribution of a number of ROR hydropower stations along the river network, and the structure of the local mini-grids. We then use downscaled outputs from three general circulation models GCMs (RCPs 2.6, 4.5, 8.5) from the Intergovernmental Panel on Climate Change IPCC AR5, to assess the performance of the system under future modified hydrological conditions. We find that our proposed method is efficient in shaping ROR systems, with the target of the largest possible coverage (93%), and of the least price (0.068 € kWh−1 on average). We demonstrate also that under the projected hydrological regimes until 2100, worse conditions than now may occur, especially for plants with small drainage areas. Days with energy shortage may reach up to nf = 38 per year on average (against nf = 24 now), while the maximum daily energy deficit may reach as high as edef% = 40% (against edef% = 20% now). We demonstrate that our originally proposed method for ROR grid design may represent a major contribution towards the proper development of distributed hydropower production in the area. Our results may contribute to improve energy supply, and living conditions within the Dudh Koshi river. It is likely that our approach may be applied in Nepal generally. Impending climate change may require adaptation in time, including the use of other sources which are as clean as possible, to limit pollution. Our Poli-ROR method for grid optimization may be of use for water managers, and scientists with an interest in the design of optimal hydropower schemes in topographically complex catchments.