Objective: Scientific literacy is essential for pre-service biology teachers, yet evidence on the independent and combined contributions of epistemological beliefs and self-efficacy remains limited and inconsistent, particularly in the Nigerian context. This study investigated the influence of epistemological beliefs and self-efficacy on the scientific literacy of pre-service biology teachers in public universities in Osun State, Nigeria. Method: A descriptive survey design with a two-stage sampling procedure was employed. Two public universities were purposively selected, and 129 pre-service biology teachers were randomly sampled from a population of 255. Data were collected using the Epistemological Questionnaires Items (EQI), Self-efficacy Scale (SeS), and Scientific Literacy Scale (SLS), with reliability coefficients of 0.80, 0.87, and 0.77, respectively. Simple and multiple linear regression analyses were conducted at the 0.05 significance level. Results: The epistemological-belief score significantly and negatively predicted scientific literacy (B = -0.040, β = -0.266, t = -3.108, p = 0.002, R² = 0.071), whereas self-efficacy was not a significant predictor (B = 0.010, β = 0.097, t = 1.098, p = 0.274, R² = 0.009). The reported statistics for the joint model were internally inconsistent; therefore, no valid conclusion regarding the combined effect can be made without re-analysis of the original dataset. Novelty: The study contributes context-specific evidence that epistemological beliefs and self-efficacy do not operate as uniformly positive direct predictors of scientific literacy. It highlights the need to interpret epistemological-belief scores according to their multidimensional scoring orientation and to examine self-efficacy within more differentiated explanatory models.