Background. The diagnosis and treatment of head and neck tumors present significant challenges due to their infiltrative nature and diagnostic hindrances such as the blood–brain barrier. The intricate anatomy of the head and neck region also complicates the clear identification of tumor boundaries and assessment of tumor characteristics. Aim. This review aims to explore the efficacy of molecular imaging techniques that employ targeted contrast agents in head and neck cancer imaging. Head and neck cancer imaging benefits significantly from the combined advantages of CT and MRI. CT excels in providing swift, high-contrast images, enabling the accurate localization of tumors, while MRI offers superior soft tissue resolution, contributing to the detailed evaluation of tumor morphology in this region of the body. Many of these novel contrast agents have integration of dual-modal, triple-modal, or even dual-tissue targeting imaging, which have expanded the horizons of molecular imaging. Emerging contrast agents for the purpose of MRI and CT also include the widely used standards in imaging such as gadolinium and iodine-based agents, respectively, but with peptide, polypeptide, or polymeric functionalizations. Relevance for patients. For patients, the development and use of these targeted contrast agents have potentially significant implications. They benefit from the enhanced accuracy of tumor detection and characterization, which are critical for effective treatment planning. Additionally, these agents offer improved imaging contrast with the added benefit of reduced toxicity and bioaccumulation. The summarization of preclinical nanoparticle research in this review serves as a valuable resource for scientists and students working towards advancing tumor diagnosis and treatment with targeted contrast agents.