When evaluating the public health effects of novel tobacco products, such as candidate modified risk tobacco products (cMRTPs), risk perceptions are important as they are potential determinants of product use. In this paper, we describe the development of a conceptual framework of perceived risks associated with the use of tobacco and nicotine-containing products. We conducted a literature review, held 12 focus group discussions in the USA, and elicited expert opinions to identify key concepts related to risk perceptions of tobacco and nicotine-containing products. The literature review, focus groups, and expert opinions provided evidence for triangulation, revealing that the key concepts could form the basis of a conceptual framework in 5 domains: perceived health risk to self, perceived health risk to others, perceived addiction risk, perceived social risk, and perceived practical risk. This new framework can be used to support population-based and clinical research, establish the validity of the current research strategies, and develop evidence-based guidance for the development of new self-report instruments that are needed to evaluate the public health effects of novel tobacco products.