Hypoxia, defined as the deficiency of oxygen, is a significant hallmark of cancers presenting in the majority of solid tumors. Detection of tumor hypoxia is essential in cancer diagnosis to prevent cancer progression, metastasis, and resistance to cancer therapies in clinical practices. Single-photon emission computed tomography (SPECT) is one of the methods studied and applied for hypoxia detection with the use of radiolabeled imaging agents in which ^99mTc is the common radioisotope used for radiolabeling. Nitroimidazoles are the hypoxia-targeting moieties presenting in numerous ^99mTc-radiolabeled imaging agents due to their bio-reducible ability in hypoxic environments. Recently, in addition to ^99mTc-labeled radiopharmaceuticals containing one nitroimidazole unit, there has been considerable attention given to ^99mTc-radiopharmaceuticals bearing two or more nitroimidazole units. This review summarizes the synthesis of hypoxia-targeting chelators and radiolabeling processes to produce these ^99mTcradiopharmaceuticals for SPECT imaging.