An extensive study is presented on the simulation, optimization and establishment of several hybrid RES-based building scale systems, designed to produce electricity to cover different electrical requirements. As fundamental case study, an already established system was simulated and optimized to be financially and energetically feasible for off-grid operation. Solar and wind resources along with several buffering technologies are proposed and related to the characteristics of such an investment. Moreover, based on a comparative feasibility study for systems simulated on several Greek islands, the role of grid connection was investigated. Finally, a laboratory-scale system was built to validate the theoretical predictions with experimental measurements, thus identifying the validity of the HOMER simulation platform.