The Alpine regions have faced a multitude of changes in recent years, and further critical transformations are expected in the years to come. This process is driven primarily by the impacts of climate change, that has brought substantial alterations to the hydrologic cycle increasing the frequency and severity of extreme events. Together with the evolution of the climate, other key factors will be crucial in defining the future evolution of Alpine regions, such as socio-economic, technological, and legislative aspects. These transformations will upset the status quo, affecting several sectors, from agriculture to tourism, from ecosystem to hydropower generation and flood prevention. In this context, decision makers are required to adopt multi-sector and multi-purpose water portfolios, also considering the different aspects of future scenarios. In the present research, we analyze multiple adaptation strategies for the Adda river basin, a complex Alpine water system in the Northern Italy. This system encompasses various elements, including many upstream reservoirs used for hydropower production, Lake Como (where the main interests are represented by tourism, aquatic ecosystems, and flood prevention), and several agricultural and power generation districts downstream. The portfolios are formulated by combining i) the renegotiation of the hydropower licenses, ii) the redefinition of Lake Como flooding threshold, operating limits and management policies, and iii) adoption of different technological innovations and sustainable practices for irrigation. The combination of these measures allows for significant benefits compared to the current situation, with improvements in flood control (+92%), summertime deficits downstream (+69%), and Lake low levels (+40%), and a slight decrease in hydropower revenue (-1.4%). The study of the impact of climate change (using three different projections) and socio-economic factors (considering two electricity price scenarios) shows that, in the mid and long term, the system is highly vulnerable. However, the proposed portfolio represents an effective adaptation strategy.