Among the various classes of pharmaceuticals, antineoplastic agents require particular attention. This work investigates the degradation of the anticancer drugs anastrozole (ANZ) and methotrexate (MTX) by the solar photo-Fenton (SPF) process under different experimental conditions and in different aqueous matrices. Tentative identification of the treatment transformation products (TPs) was performed by suspect screening, employing a purpose-built database containing thirty-three TPs from ANZ and MTX. The experimental condition that achieves the most favorable degradation of ANZ and MTX in real hospital wastewater was pH 5 and multiples additions of Fe2+. This condition provided a reduction of ANZ and MTX of 30 % and 70 %, respectively. Eighteen MTX TPs and five ANZ TPs were tentatively identified in the analyzed samples. After tentative identification, quantitative structure-activity relationship ((Q)SAR) in silico methods were used to predict eight endpoints of environmental risk of the selected analytes. When different possible structures could be proposed, all the possibilities were considered, resulting in fifty-nine structures evaluated. TOPSIS multicriteria decision-making method was used to rank the compounds according to their environmental concern, based on (Q)SAR predictions. As main results, TOPSIS ranking showed that all ANZ TPs and most MTX TPs showed higher environmental risk potential than the parent compounds. The findings highlighted the importance of qualitative tentative identification of TPs and their monitoring throughout treatments, as well as risk assessment using various endpoints simultaneously. The proposed approach can provide objective and holistic evaluation of treatment processes.