The integration of science, technology, engineering, and mathematics (STEM) education in various fields of knowledge is needed to enhance the country’s economic development. STEM education is essential in developing technology towards the Industrial Revolution 4.0 (IR4.0) era. However, in many countries, especially in Indonesia, students are less interested in STEM subjects. This study aims to identify the differences and interactions of student interest in STEM based on parental education and gender. This study uses a quantitative method involving 150 secondary school students at Simanosor Julu, Medan, Indonesia. The results of data analysis based on the mean score indicated that there are differences in students’ interest in STEM-based on gender and parental education. The mean score of male students, based on parental education at the university level, is higher than female students. It is recommended that there are additional study more deeply the STEM interests of students based on (a) social-economic status, (b) rural and urban schools, (c) the relationship between the two variables, and (d) involves students with more numbers.