The mammalian target of rapamycin (mTOR) is a critical regulator of cellular functions, including protein synthesis, cell growth, survival, and apoptosis. It integrates diverse environmental signals and is involved in various diseases, including metabolic disorders, cancer, and aging. mTOR dysregulation is implicated in the onset and progression of these conditions. mTOR exists in two complexes, mTORC1 and mTORC2, each with distinct roles. mTORC1 is primarily activated by growth factors and nutrients, regulating cell growth and autophagy, while mTORC2 is less sensitive to nutrients and is involved in actin cytoskeleton regulation and glucose uptake. mTOR inhibitors, such as rapamycin and everolimus, have shown therapeutic potential in treating cancers and other diseases. However, first-generation inhibitors partially inhibit mTOR signaling, leading to limited efficacy. Second-generation inhibitors, which are ATP-competitive and target both mTORC1 and mTORC2, have shown more complete inhibition. Third-generation inhibitors, such as RapaLink-1, have demonstrated improved efficacy in organ transplantation. mTOR signaling is also crucial for aging, with its inhibition promoting longevity by enhancing autophagy and reducing cellular stress. The development of more effective mTOR inhibitors is essential for treating diseases associated with mTOR dysregulation. This review highlights the importance of mTOR signaling in metabolic diseases, cancer, and aging, and emphasizes the need for further research into next-generation mTOR inhibitors and combination therapies.The mammalian target of rapamycin (mTOR) is a critical regulator of cellular functions, including protein synthesis, cell growth, survival, and apoptosis. It integrates diverse environmental signals and is involved in various diseases, including metabolic disorders, cancer, and aging. mTOR dysregulation is implicated in the onset and progression of these conditions. mTOR exists in two complexes, mTORC1 and mTORC2, each with distinct roles. mTORC1 is primarily activated by growth factors and nutrients, regulating cell growth and autophagy, while mTORC2 is less sensitive to nutrients and is involved in actin cytoskeleton regulation and glucose uptake. mTOR inhibitors, such as rapamycin and everolimus, have shown therapeutic potential in treating cancers and other diseases. However, first-generation inhibitors partially inhibit mTOR signaling, leading to limited efficacy. Second-generation inhibitors, which are ATP-competitive and target both mTORC1 and mTORC2, have shown more complete inhibition. Third-generation inhibitors, such as RapaLink-1, have demonstrated improved efficacy in organ transplantation. mTOR signaling is also crucial for aging, with its inhibition promoting longevity by enhancing autophagy and reducing cellular stress. The development of more effective mTOR inhibitors is essential for treating diseases associated with mTOR dysregulation. This review highlights the importance of mTOR signaling in metabolic diseases, cancer, and aging, and emphasizes the need for further research into next-generation mTOR inhibitors and combination therapies.