Oral cancer and Oral Potentially Malignant Disorders (OPMD) are major health problems in South and Southeast Asia. To describe and discuss the clinical aspects of Oral Cancer and OPMD in South and Southeast Asia. Literature review of concepts and data over the last four decades. Asian countries account for about two-thirds of new cases of oral cancer (OC) globally, with the highest burden in the South and Southeast Asian countries, including Pakistan and India. Habits, dietary patterns, socioeconomic status, and access to routine dental care play a crucial role in defining the demographics and clinical presentation of OC in these regions and significantly influence the morbidity and mortality of the disease. This region sees the use of different types of tobacco with or without areca nut (AN), such as pan masala, gutka, gul, snuff, mawa, and mishri. Tobacco use is high among men in Sri Lanka, Myanmar, Maldives, Bangladesh, Nepal, India and Bhutan. Areca nut is the fourth most common addictive substance globally and is frequently used in South and Southeast Asian countries, including Southeast China, Hainan Island, India, Taiwan, and the Pacific Islands, and immigrants from these regions in Africa, Europe, and North America. The use of these products results in mucosal alterations with varied clinical presentation of Oral Potentially Malignant Disorders (OPMDs) and OC. We discuss here the different types of OPMD and OC, the diagnostic aids and their relevance in clinical practice, and factors that influence their prognosis.