Dual modality molecular imaging can capture concurrent molecular events and evaluate therapeutic efficacy from uniquely different perspectives based on different molecular targets. In this work, dual modality tomographic imaging, (18) F-fluorodeoxyglucose based positron emission tomography and subsurface fluorescence molecular tomography ([(18) F]FDG-PET/subsurface FMT), is proposed to monitor tumor response to cisplatin on a mouse xenograft model in vivo. One mouse was administered with cisplatin (1.0 mg/kg) by intraperitoneal injection once every day for 14 days, and another mouse was administered with saline to serve as the control. Dual modality [(18) F]FDG-PET/subsurface FMT imaging was conducted on days 0, 2, 5, 9, 15, and 22. In vivo imaging and quantitative analysis demonstrated the feasibility of [(18) F]FDG-PET/subsurface FMT imaging in tracking the changes of [(18) F]FDG tumor uptake and amount of red fluorescent protein (RFP) synthesized by tumor cells in the same mouse simultaneously. Dual modality [(18) F]FDG-PET/subsurface FMT imaging may thus provide a powerful tool for better understanding disease progress and treatment evaluation from different perspectives.