In this study, a combination of the high detectability and specificity of the SERS technique with powerful chemometric tools was used to obtain hyperspectral images in order to assess the chemical distribution of the components of polymeric microfilms loaded with paracetamol as active principle. Four microfilms with drug content ranging between 5.42 and 18.62% were fabricated directly over nanostructured gold substrates and spectra were acquired over an area of 4 × 4 mm. Chemical images were first built following a qualitative approach by applying principal component analysis (PCA) and calculating correlation coefficients. With the algorithm multivariate curve resolution-alternating least squares (MCR-ALS), the mean concentrations of all components were calculated with relative error values between 3.5 and 4.9% for paracetamol. With the proposed methodology, both qualitative and quantitative assessments of the distribution of constituents of polymeric microfilms were successfully performed. In addition, physical-chemistry interactions among them could be also analyzed.