Nitromidazoles are relevant compounds of multidisciplinary interest, and knowledge of their physical chemical parameters as well as their decomposition under photon irradiation is needed. Here we report an experimental and theoretical study of the mechanisms of VUV photo fragmentation of 2- and 4(5)-nitromidazoles, compounds used as radiosensitizers in conjunction with radiotherapy as well as high-energy density materials. Photoelectron photoion coincidence experiments, measurements of the appearance energies of the most important ionic fragments, density functional theory, and single-point coupled cluster calculations have been used to provide an overall insight into the energetics and structure of the different ionic/neutral products of the fragmentation processes. The results show that these compounds can be an efficient source of relevant CO, HCN, NO, and NO2 molecules and produce ions of particular astrophysical interest, like the isomers of azirinyl cation (m/z 40), predicted to exist in the interstellar medium, and protonated hydrogen cyanide (m/z 28).