Background <p>Academic performance in nursing and midwifery students is a significant feature determining the quality of training and workforce readiness. Although some studies have emphasised the admission process and institutional factors as the main determinants of academic performance, less has been revealed about the association of pre-tertiary educational background with academic performance after the students’ enrolment. Few studies in sub-Saharan Africa have integrated objective pre-tertiary academic indicators with psychological preparedness constructs within a theoretically grounded framework.</p> Objective <p>This study assessed the link between senior high school (SHS) background and academic readiness and the academic performance of nursing and midwifery students in Ghana.</p> Methods <p>A cross-sectional study was conducted among 345 nursing and midwifery students at a public training institution in Ghana. Data were collected using a structured questionnaire capturing socio-demographic characteristics, SHS background, academic preparedness, institutional support, and academic outcomes. Last-semester grade point average (GPA) was analysed as an ordered categorical outcome using ordinal logistic regression.</p> Results <p>Participants reported moderate levels of academic preparedness, with mean scores of 3.55 (SD = 0.55) for science self-efficacy, 3.38 (SD = 0.54) for language proficiency, 3.63 (SD = 0.49) for study strategies, 3.73 (SD = 0.54) for grit and time management, and 3.68 (SD = 0.58) for institutional support. The ordinal regression model indicated a good general fit to the data (Likelihood Ratio χ² = 374.64, <i>p</i> &lt; .001). When compared to the other two circumstances, the student’s background was found to be a predictor of their academic performance, as the General Science (<i>p</i> &lt; .001) and Agricultural Science (<i>p</i> = .010) students’ occurrences of having the better GPA categories were higher than their counterparts. On the other hand, the composite WASSCE scores, science self-efficacy self-reported measures, and academic language proficiency, study strategies, grit, time management, and institutional support were not associated with GPA after adjustment independently.</p> Conclusion <p>Nursing and midwifery students’ steps up in education seem to be achieved mostly through different paths of schooling-level possibilities rather than through individually felt readiness. Additionally, the integration of the results of this study with proper coordination between undergraduate and secondary education will significantly enhance the production of efficient learning outcomes and strengthen the nursing profession.</p>