Nowadays, buildings are responsible for the 40% of energy consumption in the European Union, with energy up to 68% being coherent with thermal loads. Acknowledging the great potential of building sector, a substantial amount of the current building inventory must be refurbished, based on the trade-offs between energy and thermal comfort. To this effect, this study investigates the impact of retrofitting measures in residential envelope for areas experience Mediterranean climate. Seven detached houses, located in Cyprus, were modelled, investigating 253 parameters of envelope interventions and also, 7,056 combinations of these measures. In general, the findings revealed a seasonal performance variation of interventions with regards to the outdoor climate. The application of roof insulation determined as the most economic viable solution during retrofitting (single interventions), achieving a reduction up to 25% of annual energy consumption with enhancement of the indoor thermal environment. In the perspective of synergies between interventions, the application of roof and external walls thermal insulation with upgrade of glazing system with double Low-E demonstrated exemplary levels of performance decreasing on average energy consumption up to 38%.The findings of this research will contribute on the development of guidelines for designers and house builders for a perceptual retrofitting of existing residential envelopes in Cyprus and also, for countries experiencing the Mediterranean climate.