Cancer prevention, screening, and early detection play an integral role in cancer incidence and outcomes. It is estimated that 30% to 50% of cancers worldwide are preventable, and it is well established that early detection of many cancers is associated with improved treatment outcomes. A recent NCCN Policy Summit: Reducing the Cancer Burden Through Prevention and Early Detection brought together healthcare providers, payers, policymakers, patient advocates, industry representatives, and technology representatives to explore challenges, triumphs, and outstanding questions surrounding current practices. Keynotes were delivered by Dr. Lisa Richardson, Director of the Division of Cancer Prevention and Control within the CDC, and Dr. Danielle Carnival, White House Cancer Moonshot Coordinator. Dr. Richardson focused on the field of public health, translating its utility in preventing and diagnosing cancer in the United States, while Dr. Carnival discussed ambitious goals by the Cancer Moonshot in reducing the cancer burden. Panelists highlighted characteristics of high-impact prevention and early detection programs, including how genetic testing has impacted this space. Existing programs are often challenged due to limitations in data, as well as financial, structural, and social barriers to motivating individuals to act on recommendations. Despite these barriers, we can learn from highly successful programs and should apply proven attributes, such as community engagement, more broadly.