This study aims to determine the role of worldview perspective on science students’ decision-making process by a socio-scientific issue-based instruction through an integrated Science Technology Engineering and Mathematics (STEM) education. Understanding the decision-making process in complex themed learning is one of the most important instruments in understanding the way students think. The participants were one hundred and nine junior-high-school students from two different schools. Furthermore, the method used was a pre-experimental design with two collective groups, namely the pre-and posttest, starting with an educational study design. The results showed that there was a different perspective pattern based on the worldview perspective on students’ initial decisions. Furthermore, interventions with socio-scientific issues (SSI) based instruction through integrated STEM education provided significant dynamics of change in the final science decision made by the students on the basis of a worldview perspective and gender. Some practical implications were extremely discussed, such as the crucial role of the teacher during a complex lesson topic. Therefore, this study makes an indispensable contribution to the development of the knowledge of science teaching practice, especially on how a decision-making process occurs by a socio-scientific issue-based instruction through integrated STEM education.