As energy saving is so important in buildings nowadays, envelopes performances have to be more efficient and have to deal with more obligations, such as moisture accumulation and mould growth. This study relies on an experimental wooden frame house exposed to the natural conditions of Grenoble, France. It has been widely instrumented so the wall’s temperature and humidity is monitored at different depths. As a consequence, complete dataset are available and can be used to validate numerical model. In this work, an existing numerical model named HAM-Tolls has been used to simulate the heat, air and moisture coupled transfers at the building scale. The method developed here consists in validating the numerical model step by step, with studying specific transfers separately. The first step deals with heat and mass transfers across the walls. Then, the heat transfers across a ventilated air gap and the air change rate under natural conditions have been studied much in detail. The final step of this works consists in simulating simultaneously every transfer at the building scale. This latest simulation’s results were compared both on a local and on a global point of view with the measurements. As they were found to be in good agreement, this allows concluding on the methodology efficiency, the validity of the modelling assumption and gives good hope with extending this methodology to other studies. Specifically, the simulation tool is able to predict correctly the average temperature and humidity content within the walls. Therefore, it should be suitable with estimating the wall components influence on the wall durability, its energy efficiency and its impact on the occupant’s thermal comfort.