Background: Tuberculosis (TB) has continued to be a major health concern to man and has affected majority of the population around the world. In the World Health Organisation (WHO)’s estimate, Nigeria is second in Africa and seventh in the world with regard to cases. Since Lagos is the most populous state in Nigeria, it has made a high number of tuberculosis cases. Since there is no cure for TB without taking the prescription drugs, noncompliance has been as frequent as the disease, leading to treatment failure, drug resistant TB and increased cost of healthcare. The e-refill prescription system which is an electronic prescription refill system is targeted to increase medical compliance amongst TB patients consequently improving overall health. Aim: The purpose of this study is therefore to evaluate the factors which determine medication compliance among TB patients on the e-refill prescription in health facilities in Lagos state. Setting: Various healthcare facilities across Lagos. Methodology: This study employed the cross-sectional method. For sampling, we opted for a purposive sampling approach to select the patients. The sample size, determined using the Kish formula, comprised approximately 338 TB patients. In order to collect data on critical factors such as patient’s satisfaction, factors influencing e-refill medication adherence, and the willingness to adopt the e-refill system, this study made use of in-depth interview and semi- structured question. Furthermore, the collected data was analysed with SPSS software, with two team members independently coding the interview transcripts to identify emerging themes and resolve discrepancies through consensus discussions. Results: A large proportion of the participants fell between the ages of 28 to 38 years (45.9%), (53.0%) were married, and the Yoruba ethnic group dominated the population at (49.4%). Most patients received care from government- owned facilities (75.1%). 68.6% considered medical adherence important. Of factors influencing medical adherence, (47%) said that forgetfulness often affected their adherence, and (23.7%) cited the side effect. Of those surveyed, 54.4% expressed interest in using the e- Refill system, and 60.7% were knowledgeable about it. Ease of use (32.8%) and system trust (29.9%) are the main variables influencing readiness to utilise the e-Refill system. Conclusion: The e-Refill system has shown potential for success in improving medication adherence among TB patients in Lagos state. However, it is important to address challenges such as limited access to healthcare and reluctance among certain patient groups need to be addressed. To get maximum result possible from the system, it is important to take steps to enhance patient engagement, address stigma associated with the illness, and ensure sustained support over the duration of the treatment. Contribution: The study highlights the significance of niche interventions geared towards promoting medication adherence and improving TB treatment outcomes in resource-constrained environments.