Although there is an invaluable growth of science and technology across the world, many young people appear to lose interest in Mathematics and science-related subjects due to poor academic achievement caused by different factors. The factors affecting students' achievement in science subjects among sub-Saharan Africa countries,including Rwanda, have been an issue for stakeholders on investigating how to improve the teaching and learning of science in basic education. In this study, a purposive cluster sampling of 261 participants, including 210 students, 23 teachers, seven head teachers, seven Sector Education Inspectors (SEIs), and 14 parents were used. Data were collected through a questionnaire addressed to learners; analyzed using SPSS via descriptive statistics. An interview was conducted with students' representatives, teachers, head teachers,Sector Education Inspectors, and focus group discussion with 14 parents which was analyzed using content analysis. The analysis indicated that key factors of low performance in science subjects include the level of teachers' education; family's economic background; availability of teaching and learning materials; distance covered by learners from home to school; learner's prior knowledge; and level of parents'education and absenteeism of learners. Thus, the above seem to affect the academic achievement of students in the advanced level of Twelve-Year Basic Education in Rwanda. Views about how to improve learning achievements in science such as equipping the laboratories, constructing more 12YBE schools in various areas to curb the problem of long distances covered by learners to and from school, training teachers on innovative teaching methods were suggested. The results informed that in-service teachers' training and parental involvement should be encouraged to track and sustain learners’ learning.