This paper presents a multiphysical numerical study of a photothermal therapy performed on a numerical phantom of a mouse head containing a glioblastoma. The study has been designed to be as realistic as possible. Heat diffusion simulations were performed on the phantom to understand the temperature evolution in the mouse head and therefore in the glioblastoma. The thermal dose has been calculated and lesions caused by heat are shown. The thermal damage on the tumor has also been quantified. To improve the effectiveness of the therapy, the photoabsorber’s concentration was increased locally, at the tumor site, to mimic the effect of using absorbing contrast agents such as nanoparticles. Photoacoustic simulations were performed in order to monitor temperature in the phantom: as the Grüneisen parameter changes with the temperature, the photoacoustic signal undergoes changes that can be linked to temperature evolution. These photoacoustic simulations were performed at different instants during the therapy and the evolution of the photoacoustic signal as a function of the spatio-temporal distribution of the temperature in the phantom was observed and quantified. We have developed in this paper a numerical tool that can be used to help defining key parameters of a photothermal therapy.