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Background: Emerging evidence suggests that positive impacts can be generated when digital health interventions are designed to be responsive to the cultural and socioeconomic context of their intended audiences., Objective: This narrative review aims to synthesize the literature about the cultural adaptation of digital health interventions. It examines how concepts of culture and context feature in design and development processes, including the methods, models, and content of these interventions, with the aim of helping researchers to make informed decisions about how to approach cultural adaptation in digital health., Methods: Literature searches for this narrative review were conducted across 4 databases. Following full-text article screening by 2 authors, 16 studies of interventions predominantly focused on the self-management of health were selected based on their detailed focus on the process of cultural adaptation. Key considerations for cultural adaptation were identified and synthesized through a qualitative narrative approach, enabling an integrative and in-depth understanding of cultural adaptation., Results: The literature demonstrates varying approaches and levels of cultural adaptation across stages of intervention development, involving considerations such as the research ethos orienting researchers, the methodologies and models used, and the resultant content adaptations. In relation to the latter, culturally appropriate and accessible user interface design and translation can be seen as particularly important in shaping the level of adaptation., Conclusions: Optimizing cultural adaptation involves linking culture with other contextual factors such as economic conditions and social systems to ensure accessibility and the sustained use of digital health interventions. Culturally humble approaches that use the involvement of a broad range of participants, experts, and other stakeholders are demonstrated to spark vital insights for content development, implementation, and evaluation., (©Aila Naderbagi, Victoria Loblay, Iqthyer Uddin Md Zahed, Mahalakshmi Ekambareshwar, Adam Poulsen, Yun J C Song, Laura Ospina-Pinillos, Michael Krausz, Mostafa Mamdouh Kamel, Ian B Hickie, Haley M LaMonica. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.07.2024.)