In practice, the quest for the optimal operation of energy systems is complicated by the simultaneous presence of operating constraints, among which the need for producing the power required by the user, and of uncertainty. The latter concept incorporates the potential inaccuracies of the models at hand but also degradation effects or unexpected changes, such as, e.g. random load changes or variations of the availability of the energy source for renewable energy systems. Since these changes affect the optimal values of the operating conditions, online adaptation is required to ensure that the system is always operated optimally. This typically implies the online solving of an optimization problem. Unfortunately, the applicability and the performances of most model-based optimization methods rely on the quality of the available model of the system under investigation. On the other hand, Real-Time Optimization (RTO) methods use the available online measurements in the optimization framework and are, thus, capable of bringing the desired self-optimizing control reaction. In this article, we show the benefits of using several RTO methods (co-) developed by the authors to energy systems through the successful application of (i) “Real-Time Optimization via Modifier Adaptation” to an experimental Solid Oxide Fuel Cells (SOFC) stack, of (ii) the recently released “SCFO-solver ” to an industrial SOFC stack, and of (iii) Dynamic RTO to a simulated tethered kite for renewable power production. It is shown how such problems can be formulated and solved and significant improvements of the performances of the three aforementioned energy systems are illustrated.