Mammalian target of rapamycin (mTOR), as an axial mediator of multiple cell growth pathways, is in connection with several other proteins that are involved in the regulation of homeostasis in the cell function. mTOR"s signaling pathway participates in and integrates a variety of environmental cues to control cancer cell and normal tissue development. mTOR and its inhibitors including the rapamycin analogues are attractive therapeutic indication to clinical trials for treating various types of cancers, with or without inhibitors of other signaling pathways. Despite the promising results in cancer treatment, low water solubility of rapamycin is shown to decrease its therapeutic efficacy. To reach an acceptable level of efficacy, high distribution and accepted dispersing of utilized drugs in control of mTOR signaling pathway, nanomaterials-based drug delivery can play an important role. Evaluation of the mechanisms and therapeutic effects of nanoparticle-based mTOR modulation can be useful in developing safe strategies in treatment of cancer. Regarding the clinical importance of mTOR deregulation in human diseases, hereby, we address the recent progress in the field of nanoparticle-based mTOR targeted therapy.