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Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy., This work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2016-75362-C3-1-R, MAT2017-83111R, and MAT2017-85617-R, by the Instituto de Salud Carlos III (PI16/00812), by the Comunidad Autonoma de Madrid (B2017/BMD-3867 RENIM-CM), and cofinanced by the European Structural and investment fund. Additional funding was provided by the European Union's Horizon 2020 FET Open programme (Grant Agreement No. 801305, NanoTBTech), the Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal project IMP18_38 (2018/0265), and also by COST action CA17140. Y.S. acknowledges a scholarship from the China Scholarship Council (No. 201806870023). I.Z.G. thanks UCM-Santander for a predoctoral contract (CT63/19-CT64/19). D.O. and I.R. acknowledge financial support from the Community of Madrid under Contract No. PEJD-2017-PRE/IND-3663, and from the Spanish Ministry of Science and Innovation through the Ramon y Cajal grant RYC2018-025253-I, Research Networks grant RED2018-102626-T and the PID2019-106211RB-I00 grant as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). D.O. and I.R. also acknowledge support from the "NoCanTher" project, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 685795. E.X. is grateful for a Juan de la Cierva Formacion scholarship (FJC2018-036734-I).