Retrofit actions in buildings are optimized through a holistic approach, which investigates the interactions among the potential energy efficiency measures (EEMs) by considering financing limitations, leading in this way to the optimum allocation of the available budget. An approach is proposed to this aim, including pre-selection of the most promising EEMs, detailed cost estimations, design of experiments (DOE) and building simulations, analysis of the effects and interactions between the measures and a multi-variable optimization. Two objective functions are regarded, the energy performance of the dwelling and the cost of the applicable EEMs. In addition to the optimum resources allocation, a strategy to reach a target energy class is formulated, securing the effective exploitation of the available funds. The approach is demonstrated in a dwelling, and reveals the complications when a holistic optimization focusing on the envelope, the machinery and the use of renewables, is simultaneously attempted. Overlapping between the EEMs and reversals in their priorities, with increasing the available budget for the retrofit, are realized.