Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical technique for imaging the skin at high resolution (∼ 1 μm), based on a combination of OCT and reflectance confocal microscopy. LC-OCT generates three-dimensional (3D) images of skin tissues with a penetration depth down to 500 μm, providing a new tool for 3D morphological characterization of the skin. Confocal Raman microspectroscopy (CRM) is an optical modality that allows for point measurement of the molecular content of a sample by probing its molecular vibrations. We have developed a method to co-localize data acquired by separate LC-OCT and CRM systems. LC-OCT allows for recording 3D morphological overview images in which points of interest (POIs) can be localized for molecular analysis using CRM. Biopsies of tattooed skin with adverse reactions were analyzed using co-localized LC-OCT and CRM. The combination of morphological and molecular information revealed the presence of tattoo ink in specific areas of the dermis. The LC-OCT-CRM co-localization provided new information on the type of ink pigment used and its abundance in different regions of the dermis. Correlation of LC-OCT and CRM information also pointed out markers of inflammation with the presence of inflammatory cells. The morpho-molecular characterization provided by the combination of LC-OCT and CRM could allow better management of tattoo reactions, and contribute to warn against the use of certain pigments in tattoos.