Early evidence of materials decay can provide diagnostic insights to conservators and scientists enhancing the overall knowledge on art materials. Limited knowledge is available on the long‐term behavior of synthetic and natural polymers used in art. This research poses the foundations for studies on organic materials suffering from autoxidation processes, using nondestructive surface enhanced Raman spectroscopy (SERS) for the detection of commonly present low molecular weight degradation products. Such products are here considered molecular markers for diagnostic investigations, and SERS allows detection limits never reached before. 3D aluminum (Al)‐coated SERS substrates are optimized for in situ sampling of artifacts, testing different reference materials, sampling strategies, and instrumental conditions. Linseed oil is an organic material widely used in art, which degradation mechanisms are well‐known. Considering that many polymeric compounds follow similar degradation pathways, linseed oil seemed an excellent model material for a wider research on SERS for polymers degradation in artworks.