The study of head and neck cancer (HNC) has been significantly enhanced by the development of 3D spheroid models, which closely replicate the in vivo tumor microenvironment (TME) by preserving cellular heterogeneity, hypoxic regions, and tumor-specific cell interactions. Traditional 2D models lack the capacity to capture these critical characteristics, which are essential for understanding tumor biology and therapeutic responses. This review summarizes recent advancements in HNC spheroid research, with a focus on their applications in drug testing, TME simulation, and therapeutic development. We discuss the role of spheroids in modeling key aspects such as drug resistance, hypoxia, cancer stem cell behavior, and epithelial-mesenchymal transition (EMT). Despite challenges, including variability and scalability limitations, 3D models hold significant promise for advancing precision medicine in HNC. We also explore the use of these models in evaluating therapeutic strategies, including chemotherapy, molecular-targeted therapies, and immunotherapy. Furthermore, we conduct a bibliometric analysis to assess research trends and identify emerging topics within the field of HNSCC and 3D tumor modeling. The ability of 3D spheroid models to predict patient-specific responses to treatment is highlighted, underscoring their potential for advancing personalized medicine. By examining key cellular processes that drive tumor progression and therapy resistance, we evaluate how effectively these models replicate tumor biology and speculate on future advancements that could further enhance their relevance in cancer research and treatme