Background Patient and public engagement is becoming recognised as important to strengthen cancer research. This means that research is conducted with, rather than to, about, or for, members of the public. When done in a non-tokenistic way, engagement has the potential to improve the quality and relevance of research findings. However, there is limited methodological guidance and understanding of how to deliver meaningful engagement at every stage of the research process. This study aims to address these gaps by exploring the experiences of cancer researchers and members of the public engaged in cancer research in the United States. Methods Qualitative interview design involving semi-structured interviews with cancer researchers (n=15) and members of the public engaged in cancer research (n=15), exploring how engagement is delivered, barriers, facilitators and its impact. Data were analysed using reflexive thematic analysis, supported by NVivo 20. A community advisory board comprising four lived experience experts who were previously involved in cancer research served as co-researchers. They come from diverse communities and have lived experience of cancer. Their contribution was throughout the entire study process, from design (including topic guides development) through data analysis and reporting. Results The findings capture the experiences of researchers and members of the public around patient and public engagement in cancer research. They identify the enablers (e.g., institutional support) and barriers (e.g., financial) to public engagement in cancer research, capture existing strategies to mitigate these barriers, and examine the impact of engagement activities on the research project, researchers and members of the public. This study offers new insights into establishing and delivering effective engagement activities. First, it highlights the importance of identifying suitable community representatives who can advise researchers on selecting appropriate members for the advisory boards. Second, it describes how the public can contribute to research throughout the engagement process, and how researchers can support them to ensure everyone has confidence to contribute fully. Third, it suggests options for public engagement when financial resources are limited. Conclusion Genuine patient and public engagement in cancer research is still evolving in the United States, with various approaches currently in use; however, there is a growing consensus that researchers should adapt their work to include public voices. This study will provide further understanding and guidance for cancer researchers on how to involve patients and the public in cancer research in an inclusive and impactful way.