In support of the efforts to combat the illegal sale and distribution of counterfeit anti-malarial drugs, we evaluated a new analytical approach for the characterization and fast screening of fake and genuine artesunate tablets using a combination of Raman spectroscopy, Spatially Offset Raman Spectroscopy (SORS) and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) imaging. Vibrational spectroscopy provided chemically specific information on the composition of the tablets; the complementary nature of Raman scattering and FTIR imaging allowed the characterization of both the overall and surface composition of the tablets. The depth-resolving power of the SORS approach provided chemically specific information on the overall composition of the tablets, non-invasively, through a variety of packaging types. Spatial imaging of the tablet surface (using ATR-FTIR) identified the location of domains of excipients and active ingredients with high sensitivity and enhanced spatial resolution. The advantages provided by a combination of SORS and ATR-FTIR imaging in this context confirm its potential for inclusion in the analytical protocol for forensic investigation of counterfeit medicines.