Nursing education institutions are responsible for quality education and training and are professionally accountable for nursing programmes of high academic standards. The majority of first and second year nursing students following the comprehensive four year nursing programme at a specific nursing education institution were academically unsuccessful in the subject biological science. The aim of the study was to explore and describe the factors influencing the academic performance of nursing students registered for the biological science subject at the specific nursing education institution.A qualitative, contextual, exploratory and descriptive design was used. Utilising an appreciative inquiry approach as a positive evaluation process, 429 nursing students participated in the study. Data were collected utilising self–reported appreciative interview schedule, field notes and reflective diary.The findings of the content analysis process revealed factors influencing the academic performance in biological science. The main factors identified were biological science content, characteristics of educators, educational strategies, resources and biological science assessments. The recommendations were suggested to involve stakeholders, namely nursing education institution management, nurse educators, nursing students and Eastern Cape Department of Health to actively play their various towards the positive academic performance of nursing students in the biological sciences nursing education institutions.