Since 2004, the wooden panel of the “Mona Lisa” painting by Leonardo da Vinci has been studied by an international research group of scientists [1,2] and several experimental campaigns have been carried out to understand its characteristics and provide information for the Artwork's conservation [3]. Among these, the implementation of its "digital twin" is here presented as a fundamental step for its conservation. Indeed, this digital twin is providing a deeper understanding of the mechanical characteristics of the panel, and after it has been accurately calibrated, it will provide the means for evaluating the stress states which the Artwork undergoes when the surrounding climatic conditions vary. Moreover, it will allow to evaluate in a non-invasive way the effects produced on the Artwork by any changes of its framing conditions, including the internal stresses or the external forces that it can bear without damage. The implementation of the digital twin, through a Nelder-Mead optimization scheme, starts from the definition of the shape of the Artwork, through optical methods [4], and the identification of the boundary conditions, through an experimental campaign based on the use of a film sensitive to pressure [5]. During the whole year, while exhibited in the conditioned display case, the panel continuously tends to deform, due to the slight variations in the surrounding environment. Its mechanical behaviour is automatically monitored and recorded every 30 minutes by an ad hoc equipment placed close to its back face: four miniature load cells (located at the four corners) measure the forces pressing it against the frame, and three displacement transducers measure its deflection at mid height. Finally, a method is here described to compare two different framing conditions, through the numerical computation of point-by-point stress and deformation differences, in order to provide information for optimizing settings and constraints to Conservators.