Precision medicine is an emerging approach for disease treatment and prevention that considers individual variability in genes, environment, and lifestyle for each person. Big data analytics (BDA) using cutting-edge technologies helps to design models that can diagnose, treat and predict diseases. In Ethiopia, healthcare service delivery faces many challenges specifically in relation to prescribing the right medicine to the right patient at the right time. Thus, patients face challenges ranging from staying on treatment plans longer, and then leaving treatment, and finally dying of complications. Therefore, the aim of this paper is to explore the trends, challenges, and opportunities of applying BDA in precision medicine globally and take lessons for Ethiopia through a systematic literature review of 19 peer reviewed articles from five databases. The findings indicated that cancer in general, epilepsy, and systemic diseases altogether are areas currently getting big attention. The challenges are attributed to the nature of health data, failure in collaboration for data sharing, ethical and legal issues, interoperability of systems, poor knowledge skills and culture, and poor infrastructure. Development of modern technologies, experimental technologies and methods, cloud computing, Internet of Things, social networks and Ethiopia’s government initiative to promote private technological firms could be an …