The theme of the study that catches our attention is the initial conceptions of learners in Science and school performance; this theme is based on the competency-based approach in force in Cameroon, which is implemented in several African countries. Insofar as learning is not the accumulation of new knowledge but a cognitive reorganization of old knowledge experienced, it is therefore a question of knowing what is the influence of initial conceptions on the academic performance of learners in science. The objective of this research was to show that taking into account the initial conceptions of learners, Biology “SVT” has a lasting influence on learning and thus on the academic performance of learners. To achieve this objective, the study uses the mixed and quasi-experimental method, where two groups of learners were used: a control group and an experimental group. The experimental group was subjected to the teaching-learning system designed for this purpose, and in which the initial conceptions of the learners were taken into account according to do with or go against. In the light of the different hypotheses adopted and the different results of this study, it can be observed that the didactic consideration of the learners' initial conceptions improves their academic performance through the data of the experimental group. In relation to the field of education, this study shows that in order to enable learners to learn and build knowledge in the long term, their initial conceptions must be taken into account in concrete didactics; Otherwise, learning will be sporadic, learners' conceptions will be significant, which will lead to a learning defect perceptible by school failure.