One of the main causes for damage of panel paintings of cultural heritage is due to the environmental micro-climatic variations. Wood science and numerical modeling may help to analyze and calibrate restoration interventions, to predict the behavior of the artwork, taking into account the individual painted panels and the conservation environment. In this article, a partitioning numerical strategy is proposed to predict by simulation the behavior of such artworks. It is based on a multiphysics partition focusing on the interactions between the different physics that are described in a thermodynamical framework. It is applied to the case study of Mona Lisa, modeled as a strongly coupled hygromechanical structure. The strategy is designed to couple two different modelings: a plate model for the mechanical behavior of the panel and 1D transverse diffusion for the moisture evolution. Copyright © 2011 John Wiley & Sons, Ltd.