Hybrid renewable energy systems, complemented by pumped hydropower storage, have become increasingly popular amidst the increase in renewable energy penetration. Such configurations are even more prosperous in remote regions that are typically not connected to the mainland power grid, where the energy independence challenge intensifies. This research focuses on the design of such systems from the perspective of establishing an optimal mix of renewable sources that takes advantage of their complementarities and synergies, combined with the versatility of pumped hydropower storage. However, this design is subject to substantial complexities, due to the multiple objectives and constraints to fulfill, on the one hand, and the inherent uncertainties, on the other, which span over all the underlying processes, i.e., external and internal. In this vein, we utilize a proposed hybrid renewable energy system layout for the Aegean Island of Sifnos, Greece, to develop and evaluate a comprehensive simulation-optimization scheme in deterministic and, eventually, stochastic settings, revealing the design problem under the umbrella of uncertainty. In particular, we account for three major uncertain elements, namely, wind velocity (natural process), energy demand (anthropogenic process), and wind-to-power conversion (internal process, expressed in terms of a probabilistic power curve). Emphasis is also given to the decision-making procedure regarding the system’s key design parameters (reservoir size and solar power capacity), which is achieved by thoroughly interpreting the uncertainty-aware optimization outcomes. Finally, since the proposed pumped hydropower storage uses the sea as the lower reservoir, additional technical challenges are addressed.