The engineering approach to analyse the hygromechanical behaviour of a panel painting requires a deep knowledge of its actual physical structure, including size, shape, wooden material's anatomy and character- istics, and responses to extemal actions such as forces or hygrothermal fluctuations. In fact, each panel is unique, different from all the others, because of numerous factors, in- cluding the intrinsic variability of the wood, the "cut" of the boards, the construction technique of the artwork, the succession of environments in which it has been main- tained, the irreversible processes developed during its existence, and the conservation interventions it has undergone over the centuries. Based on our experience, only a systematic set of experimental investiga- tions, conceived and implemented specifi- cally for the individuai artwork, can provide the information necessary to understand its conservation needs. However, experimen- tal investigations alone are not sufficient for a complete assessment of the artwork: numerical simulations integrated with the experimental tests can greatly improve the level of knowledge and provide more ex- tensive and deeper information. Moreover, following such an approach, the simulation can make it possible to explore situations of risk or modifications of the conservation situation in a totally non-invasive and risk- free way. The wooden panel ofLeonardo da Vinci's Mona Lisa has been studied by an intemational team with the aim of analysing and possibly improving its conservation conditions by combining a comprehensive set ofnon-invasively obtained experimental data with an advanced numerical modelling. The development of a Digital Twin of the pane I has hence provided a sound knowl- edge of the mechanical characteristics and behaviour ofthe panel, including the assess- ment of the risk of propagation of an ancient crack, and the evaluation of a new framing configuration.