Background: Southeast Asia (SEA), home to over 680 million people representing almost 9% of the global population, is amongst the most diverse and fastest-growing regions in the world. This study evaluates cancer incidence and mortality in Association of Southeast Asian Nations (ASEAN) countries with the goal of informing future research, health services, and cancer policy in the region. Methods: The number of new cases of and deaths from the leading cancers in the ASEAN region, colorectum including anus (ICD-10 C18-C21), liver including intrahepatic bile ducts (C22), lung including trachea and bronchus (C33-34), female breast (C50), cervix uteri (C53) and prostate (C61), were extracted from the International Agency for Research on Cancer GLOBOCAN 2022database for the 10 ASEAN countries by sex and age groups. Age-standardized incidence and mortality rates (ASIR and ASMR) per 100,000 person-years are presented. Results: In 2022, breast cancer was the most common cancer among women in all ten ASEAN countries (ASIR: Singapore 72.6, Philippines 60.3, Brunei 50.2, Malaysia 46.1, Indonesia 41.8, Vietnam 38.0, Thailand 37.4, Laos 31.6, Cambodia 25.1, Myanmar 23.4). Breast cancer was also the most common cause of cancer mortality among women in five ASEAN countries (ASMR: Philippines 21.5, Malaysia 19.3, Singapore 17.8, Vietnam 14.7, Indonesia 14.4). In Thailand for which time trends are available, ASIR has risen from 19 per 100,000 in 2000 to 37.4 per 100,000 in 2022. Lung cancer was the most common cancer among men in the Philippines (ASIR 37.7), Malaysia (ASIR 23.3), Myanmar (ASIR 21.6), and Indonesia (ASIR 21.3). Lung cancer is also the leading cause of cancer death among men in the Philippines (ASMR 33.6), Singapore (ASMR 31.9), Brunei Darussalam (ASMR 23.8), Malaysia (ASMR 20.4), Myanmar (ASMR 19.9), and Indonesia (ASMR 19.0). Lung cancer is also the leading cause of cancer death among women in Brunei Darussalam (ASMR 18.4). Liver cancer contributes the greatest incidence and mortality among men in Cambodia (ASIR 39.4, ASMR 37.2), Laos (ASIR 36.5, ASMR 36.4), Vietnam (ASIR 34.9, ASMR 33.3), and Thailand (ASIR 34.4, ASMR 33.4). Liver cancer was also the leading cause of cancer death among women in Laos (ASMR 13.5), Cambodia (ASMR 13.3), and Thailand (ASMR 12.1). Cervical cancer is the leading cause of cancer death amongst women in Myanmar (ASMR 13.4). Colorectum cancer is the most common cancer in men in Singapore (ASIR 39.4) and Brunei Darussalam (ASIR 37.7). Conclusions: In 2022, cancer incidence and mortality in SEA were driven primarily by breast cancer among women and lung cancer among men. Liver cancer drives incidence and mortality in Cambodia, Laos, Thailand, and Vietnam. Cervical cancer and colorectal cancer are also significant contributors to incidence and mortality in SEA. Regional and global collaboration is needed to improve cancer prevention, access to diagnosis and care, and research in Southeast Asia.