We develop an open-source Python software integrating flexibility needs from Variable Renewable Energies (VREs) in the development of regional energy mixes. It provides a flexible and extensible tool to researchers/engineers, and for education/outreach. It aims at evaluating and optimizing energy deployment strategies with higher shares of VRE, assessing the impact of new technologies and of climate variability and conducting sensitivity studies. Specifically, to limit the algorithm’s complexity, we avoid solving a full-mix cost-minimization problem by taking the mean and variance of the renewable production–demand ratio as proxies to balance services. Second, observations of VRE technologies being typically too short or nonexistent, the hourly demand and production are estimated from climate time series and fitted to available observations. We illustrate e4clim’s potential with an optimal recommissioning-study of the 2015 Italian PV-wind mix testing different climate data sources and strategies and assessing the impact of climate variability and the robustness of the results.