Oral cancer (OC) is increasing worldwide, and it is mostly present to clinic in the late-stage of disease. Cancer of the lips, tongue, hard palate, upper and lower gingiva, buccal mucosa, and retromolar trigone are all included in the category of oral cavity cancer. Disease symptomatology and pathological grading decides the course of treatment. Several treatment modalities either alone in combinations may be utilized for oral squamous cell carcinoma (OSCC), including surgery, radiotherapy (external beam radiotherapy/brachytherapy), and adjuvant systemic therapy (chemotherapy or immunotherapy). Cancer patients also face a greater risk of oral side effects from chemotherapy, such as slowed tissue healing, bone, and salivary gland damage and disintegration, and disruption of the normal bacterial balance in the mouth. Consequently, the economic burden of the salivary gland, oral cavity, and oropharyngeal cancers must be also known for budget allocation, designing different programs and management strategies targeting oral cancers by any healthcare institutes. This article provides a summary of the most recent research that supports the use of chemotherapy for patients with advanced illness both alone and in conjunction with radiation including its adverse events and cost burden for oral cancers.