Colorants are present in trace concentration in objects made of plastic and their identification is a methodological and analytical challenge. In conservation, the identification of colorants may allow a better understanding of colorant degradation (such as color change and fading) and provide information about the historical development, production and processing of plastics. Although micro-destructive analytical protocols are well established for the analysis of colorants, in cultural heritage, where in situ methodologies are preferred and, in some cases, mandatory, new approaches are greatly needed. In this work, an in situ multi-analytical approach is used to specifically study inorganic cadmium-based pigments that were commonly used for coloring plastics during the 20th c. First introduced as vivid artists’ pigments, cadmium-based additives were used for coloring plastics because of their exceptional performance properties. Eighteen colored polymethyl methacrylate (PMMA) samples, produced in the second half of the 20th c. by the company Plásticos do Sado (Portugal), were studied with a combination of optical microscopy, colorimetry, UV–Vis-NIR diffuse reflectance, laser-induced photoluminescence, vibrational (µ-Raman) and elemental (µ-EDXRF) spectroscopies. On the basis of complementary data, the chemical composition of most of the coloring agents employed in the acrylic samples were identified without any micro-sampling.