Photodegradation processes are of high relevance in environmental and pharmaceutical contexts, since the fate and identity of photoproducts are often linked to contamination or toxicology issues. The aim of this work is proposing a new general methodology to monitor and interpret photodegradation processes based on chromatographic and spectroscopic measurements and data fusion analysis. The new approach relies on two steps: (a) data fusion of HPLC-DAD–MS runs coming from process monitoring and analysis by soft-modeling multivariate curve resolution (MCR) to achieve the identification of photoproducts and a first insight on their kinetic behavior; and (b) data fusion of UV–vis spectroscopic monitoring data with HPLC-DAD process runs and analysis by hybrid hard- and soft-modeling MCR (HS-MCR) to complete the description of the kinetic mechanism of the process and to provide the related rate constants. These data fusions overcome limitations of previous approaches and have never been reported in real examples of process analysis. The ketoprofen photodegradation has been selected as the real case study to illustrate the possibilities of the described approach. In this particular case, a comprehensive description of the kinetics linked to the photochemical degradation of the ketoprofen, with all successive steps, related rate constants and photoproducts formed has been proposed. Four photodegradation products (3-(1-hydroperoxyethyl)benzophenone, 3-acetylbenzophenone, 3-(1-hydroxyethyl)benzophenone and 3-ethvlbenzophenone) could be resolved as a result of the decarboxylation of ketoprofen under UV light and the photodegradation process could be described with a kinetic model including parallel and consecutive reactions.