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Abstract Wooden Panel Paintings (WPPs) stand as invaluable cultural artefacts from the past. These works present an intriguing challenge in understanding their complex mechanical behaviour and ensuring their long-term preservation. The present study assumes as founding paradigm the unicity of each WPP, in terms of its material composition, historical background, physical dimensions, and the specific environmental conditions it has been subjected to over time, and their complex behaviour, which requires the knowledge of both mechanical and materials specificity. These characteristics need to be considered, and studied in-depth for each individual WPP, particularly if the aim is to develop a comprehensive understanding of its individual mechanical behaviour. The study provides new computational models calibrated to reproduce the physical and mechanical behaviour of artworks and acting as their 'digital twins'. The models developed contribute significantly to the understanding of the mechanics of these artworks, including the impact of environmental thermo-hygrometric fluctuations and the role of structural elements such as crossbeams. The results, corroborated by experimental analyses, indicate that environmental variations, both short and long term, exert specific and quantifiable effects on the WPPs, and that the presence of crossbeams significantly influences the distribution of stresses within the panel, particularly affecting the pictorial layers that are often the most susceptible to damage. In this context the generated digital twins serve as an invaluable tool, offering the potential to simulate various risk scenarios or to evaluate the effectiveness of engineered conservation interventions on the WPPs.