Reduced graphene oxide nanomesh (rGONM), as one of the recent structures of graphene with a surprisingly strong near-infrared (NIR) absorption, is used for achieving ultraefficient photothermal therapy. First, by using TiO2 nanoparticles, graphene oxide nanoplatelets (GONPs) are transformed into GONMs through photocatalytic degradation. Then rGONMs functionalized by polyethylene glycol (PEG), arginine–glycine–aspartic acid (RGD)-based peptide, and cyanine 7 (Cy7) are utilized for in vivo tumor targeting and fluorescence imaging of human glioblastoma U87MG tumors having ανβ3 integrin receptors, in mouse models. The rGONM-PEG suspension (1 μg mL−1) exhibits about 4.2- and 22.4-fold higher NIR absorption at 808 nm than rGONP-PEG and graphene oxide (GO) with lateral dimensions of ≈60 nm and ≈2 μm. In vivo fluorescence imaging demonstrates high selective tumor uptake of rGONM-PEG-Cy7-RGD in mice bearing U87MG cells. The excellent NIR absorbance and tumor targeting of rGONM-PEG-Cy7-RGD results in an ultraefficient photothermal therapy (100% tumor elimination 48 h after intravenous injection of an ultralow concentration (10 μg mL−1) of rGONM-PEG-Cy7-RGD followed by irradiation with an ultralow laser power (0.1 W cm−2) for 7 min), whereas the corresponding rGO- and rGONP-based composites do not present remarkable treatments under the same conditions. All the mice treated by rGONM-PEG-Cy7-RGD survived over 100 days, whereas the mice treated by other usual rGO-based composites were dead before 38 days. The results introduce rGONM as one of the most promising nanomaterials in developing highly desired ultraefficient photothermal therapy.