African medicine encounters distinct challenges shaped by diverse socio-cultural and healthcare contexts. Tunisia’s position in North Africa offers a pertinent case for examining these issues. A structured empirical analysis is needed to identify and understand the key contemporary issues affecting medical practice and healthcare delivery in this setting. This protocol outlines a study to empirically identify and analyse the principal issues in African medicine, using Tunisia as a case study. The primary objective is to characterise these key issues across clinical, operational, and systemic domains. Secondary objectives include assessing their perceived impact and exploring potential contributory factors within the local healthcare landscape. A mixed-methods, sequential explanatory design will be employed. The first phase will involve a cross-sectional survey of a stratified random sample of medical practitioners across multiple specialities and healthcare sectors. The second, qualitative phase will consist of in-depth, semi-structured interviews with a purposively selected sub-sample of survey participants to explore significant findings in greater detail. Data will be analysed using descriptive and inferential statistics for quantitative data and thematic analysis for qualitative data. As this is a protocol for future research, no empirical findings are available. The ‘Findings’ section of the final research article will present the analysed results. The study is expected to conclude by synthesising a coherent framework of the predominant issues in Tunisian medicine, offering an evidence-based overview relevant to the broader African context. Expected recommendations will target healthcare policymakers, hospital administrators, and medical educators. They will focus on practical interventions to address the identified systemic and operational issues. African medicine, healthcare delivery, Tunisia, mixed-methods, health systems research, medical practice. This study will provide an empirical analysis of key issues in a North African context, contributing to the literature on health system challenges within the region.