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This systematic scoping review proposed examining issues connected to TB medication non-adherence among TB patients over a long time in South Africa. Wide electronic databases and online digital libraries were searched, including medical informatics (Google Scholar, PubMed Central, Web of Science and MEDLINE) by means of the keywords:‘TB medication non-adherence, TB non-adherence and interventions, digital health strategy to end TB, program, management of TB, control, and sustainability to medication’. Various studies envisioned to address TB medication non-adherence in developing nations and South Africa among TB help seekers from 2010 to date were incorporated in data extraction. Twenty-eight innovative articles were altogether reviewed. Articles not written in English were all excluded. Factors that contributed to non-adherence were identified and discussed. Those factors linked with TB medication non-adherence were socioeconomic factors: patients-health care facilities, stigmatization, distance to facilities, poverty, lack of social support, and poor workers’ communication. Behavioural factors include smoking, getting improved some weeks into medication, drugs, improper communication on TB treatment are problems linked with non-adherence alongside additional factors. Digital interventions like the DOT, SMS, and Video reminders were identified, and the sustainability approach to long-term TB medication adherence during the TB journey was mentioned. Some digital interventions have been in use but have various limitations therefore, an innovative intervention that will be patient-centred and sustained over a …