The development of hybrid nanoscintillators is hunted for the implementation of modern detection technologies, like in high energy physics, homeland security, radioactive gas sensing, and medical imaging, as well as of the established therapies in radiation oncology, such as in X-ray activated photodynamic therapy. Engineering of the physico-chemical properties of nanoparticles (NPs) enables the manufacture of hybrids in which the conjugation of inorganic/organic components leads to increased multifunctionality and performance. However, the optimization of the properties of nanoparticles in combination with the use of ionizing radiation is not trivial: a complete knowledge on the structure, composition, physico-chemical features, and scintillation property relationships in hybrid nanomaterials is pivotal for any applications exploiting X-rays. In this paper, the design of hybrid nanoscintillators based on ZnO grown onto porous SiO2 substrates (ZnO/SiO2) has been performed in the view to create nanosystems potentially suitable in X-ray activated photodynamic therapy. Indeed, cytotoxic porphyrin dyes with increasing concentrations have been anchored on ZnO/SiO2 nanoparticles through amino-silane moieties. Chemical and structural analyses correlated with photoluminescence reveal that radiative energy transfer between ZnO and porphyrins is the principal mechanism prompting the excitation of photosensitizers. The use of soft X-ray excitation results in a further sensitization of the porphyrin emission, due to augmented energy deposition promoted by ZnO in the surroundings of the chemically bound porphyrin. This finding unveils the cruciality of the design of hybrid nanoparticles in ruling the efficacy of the interaction between ionizing radiation and inorganic/organic moieties, and thus of the final nanomaterial performances towards the foreseen application.