BackgroundDespite the widely anticipated benefits of eHealth technologies in enhancing health care service delivery, the sustainable usage of eHealth in transitional countries remains low. There is limited evidence supporting the low sustainable adoption of eHealth in low- and middle-income countries.ObjectiveThe aim of this study was to explore the facilitators and barriers to the sustainable use of eHealth solutions in low- and middle-income nations.MethodsA qualitative descriptive exploratory study was conducted in 4 African nations from September to December 2021. A semistructured interview guide was used to collect the data. Data were audio-recorded and transcribed from the local to the English language verbatim, and the audio data were transcribed. On the basis of the information gathered, we assigned codes to the data, searched for conceptual patterns, and created emerging themes. Data were analyzed thematically using OpenCode software.ResultsA total of 49 key informant interviews (10 from Tunisia, 15 from Ethiopia, 13 from Ghana, and 11 from Malawi) were conducted. About 40.8% (20/49) of the study participants were between the ages of 26 and 35 years; 73.5% (36/49) of them were male participants; and 71.4% (35/49) of them had a master’s degree or higher in their educational background. Additionally, the study participants' work experience ranged from 2 to 35 years. Based on the data we gathered, we identified 5 themes: organizational, technology and technological infrastructure, human factors, economy or funding, and policy and regulations.ConclusionsThis study explores potential facilitators and barriers to long-term eHealth solution implementation. Addressing barriers early in the implementation process can aid in the development of eHealth solutions that will better fulfill the demands of end users. Therefore, focusing on potential challenges would enhance the sustainability of eHealth solutions in low- and middle-income countries.