This study focuses on teaching and learning science in three secondary public school classrooms with mostly culturally marginalized students from Gurung and Magar communities in a semirural district in Nepal. The study aims to understand how three science teachers in different schools engage students in culturally relevant transformative science learning. I use a constructivist case study design. Data were collected through 18 classroom observations, three interviews with science teachers, and a student focus group interview. Analysis of the data showed that culturally marginalized students are experts in the cultural knowledge they bring into the classroom, science teachers felt ambivalence between culturally relevant science and success in tests, and science teachers showed a need for greater pedagogical skills in cultural relevancy. The study suggests a need for focused and intentional culturally relevant courses in science teacher education programs and professional development. Educating teachers for more transformative and relational science teaching will support embedding cultural knowledge and values in classroom teaching and curriculum.