Organic chemistry is a mandatory component of chemistry II and chemistry III within the curriculum for pre-service chemistry teachers (PSCTs) pursuing a degree in chemistry teaching. The organic chemistry course sequence is well recognized as challenging and unapproachable for students, despite its significant relevance and impact across several sectors. While efforts have been made to recognize and deal with challenges faced by students in the cognitive and psychomotor aspects, there has been less attention given to identifying PSCTs’ conceptual difficulties and misconceptions of organic chemistry. This includes the subsequent strategies to design instructions to enhance students’ learning experiences, which are crucial elements in addressing their achievements in organic chemistry. The study aimed to identify the conceptual difficulties and misconceptions encountered by PSCTs in organohalides and stereochemistry. Furthermore, the study aimed to suggest strategies to enhance PSCTs’ understanding of the course. The study was situated within the theoretical framework of constructivism and employed an interpretivist qualitative case study design. The population under study consisted of all individuals who were enrolled in the Bachelor of Education program within the faculty of educational sciences. A cohort of 33 whole-class PSCTs who had registered for the chemistry III course, where organohalides and stereochemistry were taught as units, were purposefully selected to participate in the study. The main instruments were document analysis, formal written tests, and interviews. Data were analyzed using thematic analysis. The study revealed that PSCTs encountered difficulties when attempting to solve problems related to organohalides and stereochemistry. In addition, PSCTs had misconceptions about these concepts. The study, therefore, recommends the implementation of suitable and appropriate instructional strategies to enhance PSCTs’ conceptual understanding and reduce misconceptions.