This report focuses on the treatment parameters leading to successful nanoshell-assisted photo-thermal therapy (NAPT). NAPT takes advantage of the strong near infrared (NIR) absorption of gold-silica nanoshells, a new class of nanoparticles with tunable optical absorptivities that are capable of passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Under controlled conditions nanoshells accumulate in tumors with superior efficiency compared to surrounding tissues. For this treatment: (1) tumors were inoculated in immune-competent mice by subcutaneous injection, (2) polyethylene glycol coated nanoshells (approximate to 150 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 - 48 hours, and (3) tumors were then extracorporeally illuminated with a collimated diode laser (808 nm, 2-6 W/cm2, 2-4 min). Nanoshell accumulations were quantitatively assessed in, tumors and surrounding tissues using neutron activation analysis for gold. In order to assess temperature elevation, laser therapies were monitored in real-time using a mid-infrared thermal sensor. NAPT resulted in complete tumor regression in > 90% of the subjects. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor treatment.