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This study investigated learning difficulties in genetics among senior secondary school students in Plateau State Central Senatorial Zone, Nigeria, with respect to gender and school location. Three research questions guided the study, and three hypotheses were tested at a 0.05 level of significance. A descriptive survey research design was adopted. The study population comprised 29,859 SS III Biology students, from which a sample of 540 students was selected using simple random sampling. The sample consisted of 280 male and 260 female students. Data were collected using the Genetics Learning Difficulties Questionnaire (GLDQ), which had a reliability coefficient of 0.87. Findings revealed that students experience varying levels of difficulty in learning genetics, with female students reporting greater learning difficulties than male students, and students in rural schools experiencing more challenges than those in urban schools. The results further indicated that both gender and school location significantly influence students' perceptions of learning difficulties in genetics. These challenges may be associated with limited access to practical learning experiences, inadequate instructional support, large class sizes, low confidence in handling abstract concepts, and unfavourable socio-educational conditions. Based on the findings, the study recommends that teachers adopt learner-centered, gender-responsive instructional strategies that actively engage students and build their confidence in understanding abstract genetic concepts. It also recommends providing well-equipped biology laboratories and adequate instructional materials, particularly in rural schools, to enhance practical learning and reduce disparities between urban and rural students.