The rapid growing of knowledge economy that relies on the advancement of ICT has changed the trend of employment and social life. Employers in this century are looking for competitive, innovative and global employees. As a consequence, students should be prepared to acquire 21 st-century skills so that they can be successful in the employment and social life. Before that, this study has examined the mastery level of the 21 st-century skills amongst science foundation programme students. This study has also investigated the relationships between former school location and gender on the mastery levels of the 21 st-century skills. A total of 240 students from two foundation colleges participated in this quantitative study. The findings indicated that the mastery level of the 21 stcentury skills was high. All subdomains of the 21 st-century skills were at a high mastery level. However, economy literacy as one of digital era literacy subdomains showed a moderate level. Meanwhile, creativity as one of the inventive thinking subdomains also showed a moderate level, and interactive communication as one of effective communication subdomains also showed a moderate level. Findings also revealed that there were no significant differences between former school location and gender on the mastery levels of the 21 st-century skills amongst science foundation programme students.