The association between exposure to indoor particulate matter (PM) and damage to cultural assets has been of primary relevance to museum conservators. PM-induced damage to the "Last Supper" painting, one of Leonardo da Vinci's most famous artworks, has been a major concern, given the location of this masterpiece inside a refectory in the city center of Milan, one of Europe's most polluted cities. To assess this risk, a one-year sampling campaign was conducted at indoor and outdoor sites of the painting's location, where time-integrated fine and coarse PM (PM(2.5) and PM(2.5-10)) samples were simultaneously collected. Findings showed that PM(2.5) and PM(2.5-10) concentrations were reduced indoors by 88 and 94% on a yearly average basis, respectively. This large reduction is mainly attributed to the efficacy of the deployed ventilation system in removing particles. Furthermore, PM(2.5) dominated indoor particle levels, with organic matter as the most abundant species. Next, the chemical mass balance model was applied to apportion primary and secondary sources to monthly indoor fine organic carbon (OC) and PM mass. Results revealed that gasoline vehicles, urban soil, and wood-smoke only contributed to an annual average of 11.2 ± 3.7% of OC mass. Tracers for these major sources had minimal infiltration factors. On the other hand, fatty acids and squalane had high indoor-to-outdoor concentration ratios with fatty acids showing a good correlation with indoor OC, implying a common indoor source.