BACKGROUND: During the COVID-19 pandemic, the provision of and access to health care have been uniquely challenging, particularly during lockdowns or when dealing with COVID-19 cases. Health care professionals have had to provide patients with the necessary health care. However, delivering health care services while reducing face-to-face interaction puts an immense strain on health systems that are already overburdened. Against this backdrop, it is now more critical than ever to ensure the accessibility of health care services. Such access has been made increasingly available through mobile health (mHealth) apps. These apps have the potential to significantly improve health care outcomes and expectations and address some of the challenges confronting health care systems worldwide. Despite the advantages of mHealth, its acceptance and adoption remain low. Hence, health care organizations must consider the perceptions and opinions of physicians if the technology is to be successfully implemented. OBJECTIVE: The objective of this systematic review was to explore and synthesize the scientific literature on the factors influencing the acceptance and adoption of mHealth among physicians during the COVID-19 pandemic. METHODS: A systematic review of the studies published between March 2020 and December 2022 was conducted using the MEDLINE, Scopus, Embase, and ProQuest databases. The database search yielded an initial sample of 455 potential publications for analysis, of which 9 (2%) met the inclusion criteria. The methodology of this review was based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). RESULTS: The factors influencing mHealth acceptance and adoption by physicians were divided into perceived barriers and perceived facilitators, which were further grouped into the following 3 major thematic categories: technological, individual, and organizational barriers and facilitators, respectively. The technological barriers were accessibility, technical issues, usefulness, and data management; individual barriers were perceived patient barriers, time and workload pressure, technical literacy, knowledge of mHealth, and peer support; and organizational barriers were financial factors, management support and engagement, data security, telemonitoring policy, and collaboration. The technological facilitators of uptake were technical factors, clinical usefulness, and data management; individual facilitators were patient-related care, intrinsic motivation, collaboration, and data sharing (individual); and organizational facilitators were workflow-related determinants, organizational financial support, recommendation of mHealth services, and evidence-based guidelines. CONCLUSIONS: This review summarized the evidence on the factors influencing mHealth acceptance and adoption by physicians during the COVID-19 pandemic. The main findings highlighted the importance of addressing organizational readiness to support physicians with adequate resources, shifting the focus from technological to patient-centered factors, and the seamless integration of mHealth into routine practice during and beyond the pandemic. TRIAL REGISTRATION: PROSPERO CRD42022356125; https://tinyurl.com/2mmhn5yu.