This study aims to test the effectiveness of a socio-scientific issue (SSI) based instruction through STEM-6E (engage, explore, explain, engineer, enrich, and evaluate). Controversial science topics (e.g. genetically modified organisms) in many countries, especially Indonesia, can be approached via integrated STEM education. One hundred and nine junior-high-school students from two different schools were involved in this study. Qualitative and quantitative data analyses were used to interpret the data obtained. Furthermore, a multi-level assessment framework (proximal and distal assessment) was employed in the quantitative analysis. The study results revealed that socio-scientific issue-based instruction by STEM-6E can probe a unique natural classroom interaction initiated by the teacher. The results also showed that both proximal and distal assessment had significant pre-test and post-test score differences (t-test value: proximal = -14.89; distal = -8.92). Practical significance from Cohen's d in the two assessments also showed a large effect (distal: d = 0.85; proximal: d = 1.42). The students' perceptions of this curriculum intervention, are extensively discussed. In conclusion, this current study's results support the claim that STEM-SSI can foster students' understanding, performance, motivation, and self-awareness in learning science. Furthermore, such findings contribute to science teachers in planning, processing, and evaluating classroom learning via controversial science topics through integrated STEM education.