Nanoparticle-mediated photothermal cancer therapy (PTT) is a treatment which creates localized damage to tumors via nanoparticles that generate heat when irradiated with near infrared light. Substantial work has been dedicated to developing efficient heat-transducing nanoparticles that can be delivered systemically to the tumor. However, less attention has been given to clinically relevant assessment methods of treatment outcome that could be used for personalizing the therapy. Here, we compare 18F-FDG positron emission tomography combined with computed tomography (PET/CT) and diffusion-weighted imaging (DWI) for early evaluation and prognosis of PTT in tumor-bearing mice using silica-gold nanoshells (NS). The NS-treated mice experienced inhibited tumor growth and significantly prolonged survival compared to control mice. One day after PTT, PET/CT and DWI scans showed a decrease in tumor 18F-FDG uptake of ~90% and an increase of ~50% in apparent diffusion coefficient (ADC) values respectively, compared to baseline. No significant changes were observed for control groups. Additionally, the changes in 18F-FDG uptake and ADC values correlated significantly with survival, demonstrating that both methods can be used for early evaluation of PTT although 18F-FDG PET/CT showed the strongest prognostic value. Based on these results, both modalities should be considered for therapy monitoring of PTT when clinically translated.