This study aimed to investigate the interrelationships among high school students’ science and mathematics achievement, attitudes towards STEM and gender. The participants of the study were 446 public high school students (240 females, 206 males) from two cities in Turkey. They were 10th, 11th, and 12th grade level students selected from two different kinds of schools which are Anatolian Religious High School and Anatolian High School. The Structural Equation Modeling (SEM) was used to determine the relationships among the variables of the study. It was found that mathematics achievement and science achievement are significantly and positively associated with students’ mathematics attitudes, and science attitudes, but negatively related to students’ attitudes towards engineering and technology. On the other hand, 21st-century skills were not found to be significantly associated with both mathematics achievement and science achievement. The results also indicated that female students had higher mathematics and science achievement scores than male students. However, male students had more interest in engineering departments. The results of the study also imply the importance of the indirect effect of attitudes towards STEM on the relationship between students’ achievement and gender.