This paper reports on an innovative out-of-school program that combined project-based learning and dual-tiered mentoring to engage middle and high school students with visual impairments (VI) in STEM. Project POEM (Project-Based Learning Opportunities and Exploration of Mentorship) supported middle and high school students between 2018 and 2022 to take part in a year-long program that included authentic STEM experiences and project-based learning and engagement with mentors who were university STEM students as well as STEM industry professionals who are blind or visually impaired. We describe the findings from a mixed-method study of middle and high school students (n = 30) and mentors (n = 33) to elucidate lessons learned. Data included pre- and post-surveys of students as well as interviews with students and mentors. By integrating accessible strategies like tactile graphics, audio-based simulations, and virtual mentoring with STEM professionals and university STEM mentors, the project fostered inclusion and enhanced students’ outcomes related to interest in STEM and STEM careers. Engaging in Project POEM increased students’ self-reported knowledge of accommodations for the workplace, their confidence in doing and presenting science, their attitudes towards STEM, their knowledge of and interest in going into a STEM career, and their confidence in engaging in the world as an individual who is blind or visually impaired. We conclude with practical recommendations based on our lessons learned for others looking to support students with visual impairments in informal education settings.