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Oral and throat cancers are heterogeneous diseases encompassing a variety of aggressive tumors of the head and neck area with high morbidity, mortality, and recurrence. Early detection, diagnosis, and treatment are essential to minimizing morbidity and mortality. Conventional treatments involve surgical resection of large tumor areas followed by nonselective radiation therapy or chemotherapy, which cause severe side effects such as mucositis, maxillary osteonecrosis, hypocellularity, nephrotoxicity, and local tissue hypoxia, which affect quality of life. Adverse effects can occur because the components in the tumor microenvironment (TME) form physical/biological barriers making difficult the diffusion of therapeutic molecules and contributing to resistance and immunosuppression. Nanotechnology offers the potential to overcome many of the problems associated with conventional treatments and the capability to detect and treat cancer simultaneously. New nano delivery strategies of bioactive molecules have greatly impacted diagnostics through the use of molecular imaging, which can reliably distinguish between malignant and benign cells. Targeting cancer and releasing therapeutic molecules in response to TME with nanoparticles lead to potent antitumor efficacy and stimulate antitumor immunity. The present chapter reviews the state of the art of nano strategies and current clinical applications to target oral and throat cancers for diagnosis and treatment.