Living walls have a great potential for the improvement of the building energy performances and the indoor comfort as well as for positive changes in dense urban areas. Despite this evidence, the design criteria have not be discussed in the available literature. This paper proposes a complete numerical approach for selecting the optimal living wall package in the Mediterranean climate areas. With a parametric analysis, the incidence of plants' type, substrate's materials, air-gap and thickness of the main materials on energy performance, thermal comfort and polluting emissions is evaluated. A multi-objective optimization is applied to a subset of solutions and for the optimal configurations the thermal field is studied by means of the computational fluid dynamic approach. The advantage of proposed method is the combined evaluations of multiple variables with simplicity in execution; for this reason it could be repeated for studying other innovative solutions. Results indicate that the better exposure for the living wall is the west one. The minimization of the cooling energy demand requires the adoption of grass species while the minimization of the heating energy demand the sedum plantings. Moreover, simulations show that the main advantage is the great incidence on the passive control of indoor microclimate with a reduction of operating hours of air-conditioning systems and of energy costs.