Despite the comprehensive applications in bioimaging, biosensing, drug/gene delivery, and tumor therapy of manganese oxide nanomaterials (MONs including MnO2, MnO, Mn2O3, Mn3O4, and MnOx) and their derivatives, a review article focusing on MON‐based nanoplatforms has not been reported yet. Herein, the representative progresses of MONs on synthesis, heterogene, properties, surface modification, toxicity, imaging, biodetection, and therapy are mainly introduced. First, five kinds of primary synthetic methods of MONs are presented, including thermal decomposition method, exfoliation strategy, permanganates reduction method, adsorption–oxidation method, and hydro/solvothermal. Second, the preparations of hollow MONs and MON‐based composite materials are summarized specially. Then, the chemical properties, surface modification, and toxicity of MONs are discussed. Next, the diagnostic applications including imaging and sensing are outlined. Finally, some representative rational designs of MONs in photodynamic therapy, photothermal therapy, chemodynamic therapy, sonodynamic therapy, radiotherapy, magnetic hyperthermia, chemotherapy, gene therapy, starvation therapy, ferroptosis, immunotherapy, and various combination therapy are highlighted.