Graffiti removal from monuments, such as statues or architecture, is becoming a priority for conservators and restorers. This operation is further complicated when the vandalism is carried out on surfaces that should be preserved, as in the case of writings or tags on historical wall paintings, or even on modern or contemporary pieces of street art. Several methods exist for graffiti removal, which include chemical, physical or biological approaches. However, traditional methodologies, such as the use of neat organic solvents, are often unsuitable. Moreover, due to the great variability of brands and formulation of commercial paints, a thorough study of materials used for graffiti and a deep knowledge of their behavior when exposed to cleaning media is currently lacking. In this contribution, we report a systematic laboratory survey on 17 different spray-can paints available on the market and commonly used for graffiti and vandalism in the Mexican area. These paints were analyzed by means of ATR FT-IR spectroscopy to characterize their composition. Several solvents, having different nature and polarity, were then used to remove the paints from glass slides. On the basis of these results, two different amphiphile-based nanostructured fluids, which present several advantages with respect to traditional cleaning methodologies, were formulated and tested on the same paint samples. Finally, the two nanostructured cleaning systems were used for the removal of vandalistic graffiti from stones decorated with red pre-Hispanic paintings in the archeological site of Ba' Cuana, Asunciòn Ixtalpetec, Oaxaca, Mexico.