This mixed-methods study examined urban adolescents’ perceptions of gender and racial/ethnic barriers to STEM (science, technology, engineering, and mathematics) success, and their meaning-making and coping regarding these experiences. The sample includes surveys from 1024 high school-aged students and interviews from 53 students. Logistic analysis showed that higher science aspirations significantly predicted perceived support for girls and women in science. Analysis of interviews showed themes of microaggressions, responses to microaggressions, and gender- and race-based support. Findings suggest participants vary in perceptions of barriers, yet are generally optimistic about overcoming such obstacles.