Today's learners will face increasing global competition for college entrance and jobs after graduation. They need to succeed in work, life and citizenship, as well as skills that are necessary for 21st century. Teaching and learning’s in the 21st century has to put the emphasis on the 4Cs, collaboration, critical thinking, creativity, and communication in the gender equality environments. Science, Technology, Engineering, and Math (STEM) Project Based Learning (PjBL) provides students to learn 4Cs skills. However, the role of gender in STEM PjBL is not clear well. So, this experimental study, run a project within an experimental group of 50 students and compare with another 57 students in the control group by employing Mixed-Design ANOVA, to evaluate changes in achievement performance differences between the genders?. We observe there were not significant differences in performance of girls and boys in the high school by running a project and measuring students’ achievement. Future study should cover the effect of gender differences on the STEM PjBL teaching method in the high school for preparing students for 21st century challenges in a broad range.