The Surgical PhotoAcoustic Nanotechnology (SPAN), a breakthrough technology is proposed mainly to change the paradigm of brain surgery. To enable a paradigm shift in brain surgery, we propose tumor-resection technology, SPAN, that combines nano neurophotonics with a real-time photoacoustic (PA) imager. This combined approach of cellular level PA image-guided surgery with in-situ photothermal ablation of residual tumor cells will result in a novel paradigm for brain tumor surgery. This goal will be realized through the integration of the first targeted magnetic resonance (MR)-PA-fluorescence (Fl) triple modality contrast agents for glioma tumor with a unique invention of hand-held real-time photoacoustic system (HARP) to yield the SPAN platform, which offers rapid response with tunable imaging depth (0.3-2 cm) and resolution (10-100 µm) for tumor margin/infiltrates identification and real-time imageguided tumor resection. The combination of contrast agents and the HARP system will yield the SPAN platform, offering for the first time the possibility to conduct real-time image-guided surgery with cellular resolution, which will shed light on further translational research to improve the lifespan of cancer patients.