Overconsumption of alcohol and tobacco are regarded as two of the main risk factors for head and neck cancer (HNC). Human papillomaviruses (HPVs) are the cause of approximately 25% of HNC cases globally. The number of HPV + HNC is rising, even while occurrences of alcohol, cigarette, and tobacco-associated HNC have decreased (by 50%) in the industrialized world as a result of reduced smoking and alcohol usage. While the numbers of OSCC and LSCC have barely changed over the past 50 years, the number of OPSSCs as a result of HPV infections has increased by more than 225%. Head and neck cancer (HNC) was traditionally believed to be associated with over consumption of alcohol and tobacco use. The etiology, clinic-epidemiology, and pathogenesis of head and neck cancer present significant challenges in the field of oncology. Shedding a new light of molecular event, identifying the new predictive, and diagnostic factors are important tasks for clinical scientists to explore further to overcome this big challenge. In the present review, we explored the various avenues like age old traditional approach, to recent theranostic avenues to not yet explored artificial intelligence-based pathomics data mining, to overcome head and neck cancer. Currently, only Epidermal growth factor receptor (EGFR) inhibitors have been approved as targeted therapeutics for HNSCC, while other more targeted treatments are being tested in clinical studies. Thus, based on earlier research findings, we provide an overview of the risk factors, qualitative and quantitative diagnosis, current advanced therapy protocols, integrative medicine, treatment strategies that target molecular pathways for head and neck cancer. In this review article, we show the risk factors, diagnosis, and management of HNSCC.