Digital technologies are increasingly being used to deliver health care services and promote public health. Mobile wireless technologies or mobile health (mHealth) technologies are particularly relevant owing to their ease of use, broad reach, and wide acceptance. Unlike developed countries, Sub-Saharan Africa experiences more challenges and obstacles when it comes to deploying, using, and expanding mHealth systems. In addition to barriers, there are enabling factors that could be exploited for the design, implementation, and scaling up of mHealth systems. Sub-Saharan Africa may require tailored solutions that address the specific challenges facing the region. The overall aim of this study was to identify the barriers and enablers for using mHealth systems in Sub-Saharan Africa from the perspectives of patients, physicians, and health care executives. Multi-level and multi-actor in-depth semistructured interviews were employed to qualitatively explore the barriers and enablers of the use of mHealth systems. Data were collected from patients, physicians, and health care executives. The interviews were audio recorded, transcribed verbatim, translated, and coded. Thematic analysis methodology was adopted, and NVivo software was used for the data analysis. Through this rigorous study, a total of 137 determinants were identified. Of these determinants, 68 were identified as barriers and 69 were identified as enablers. Perceived barriers in patients included lack of awareness about mHealth systems and language barriers. Perceived enablers in patients included need for automated tools for health monitoring and an increasing literacy level of the society. According to physicians, barriers included lack of available digital health systems in the local context and concern about patients' mHealth capabilities, while enablers included the perceived usefulness in reducing workload and improving health care service quality, as well as the availability of mobile devices and the internet. As perceived by health care executives, barriers included competing priorities alongside digitalization in the health sector and lack of interoperability and complete digitalization of implemented digital health systems, while enablers included the perceived usefulness of digitalization for the survival of the highly overloaded health care system and the abundance of educated manpower specializing in technology. mHealth systems in Sub-Saharan Africa are hindered and facilitated by various factors. Common barriers and enablers were identified by patients, physicians, and health care executives. To promote uptake, all relevant stakeholders must actively mitigate the barriers. This study identified a promising outlook for mHealth in Sub-Saharan Africa, despite the present barriers. Opportunities exist for successful integration into health care systems, and a user-centered design is crucial for maximum uptake.