Encouraging women to go into Science and Technology (S&T) careers should start with the young girls. In developing countries, such as Nigeria, girls experience challenges in studying science and technological subjects and pursuing careers in these professions. The study identifies factors that inhibit Nigerian girls from undertaking careers in S&T. A sample of 228 Nigerian Senior Secondary School girls was used for the study. A “Female Students Science and Technology Inhibitions Questionnaire” (FSSTIQ) was used to elicit responses from the girls on conceptual, psychological and physical inhibitions to their studying S&T subjects. Percentages, mean and standard deviation were used to describe the data obtained. The results reveal that the major conceptual, psychological and physical problems the girls encountered were mathematical concepts, perception of S&T subjects as being difficult, and inadequate time to study. A “Differentiated Mentoring” approach is recommended for engendering effective mentoring of school girls interested in pursuing science and technology careers.