An integrated spectroscopic study of painted plaster fragments of the Punic-Hellenistic period (4th-1st century BCE) from the Lilybaeum archaeological site in Sicily is presented. Elemental and molecular composition of the painted wall fragments is obtained via ED-XRF and FTIR spectroscopies. This study is the first ever performed on finds from Lilybaeum urban area. A wide colour palette is identified examining a significant set of 14 polychrome wall plaster fragments. Hematite, orpiment, massicot, green earths, Egyptian blue, and manganese black are discovered. Based on interdisciplinarity, this work spans from chemistry/physics to archaeology through the interpretation of the spectroscopic results in the ancient Mediterranean context. The methodological approach used may be extended to other similar projects.