Currently, computer-based laboratory environments are widely used in inquiry-based activities motivating and enabling students to experience the forefront of scientific studies such as nanoscience. This study focused on developing a hands-on computer-based nanotechnology inquiry learning module. A series of hands-on open-inquiry experiments were created to enhance student learning about self-cleaning surfaces involving the nanoscale level. A secondary focus, this study aimed to evaluate the effectiveness of learning nanoscience relative to gender differences and its effects on student motivation. Forty-six eleventh-grade public school students in Thailand participated in this study. They were given a questionnaire with 25 items to rate their nanoscience motivations before and after undergoing the learning module. Subscale scores were produced on five dimensions: intrinsic motivation; career motivation; self-determination; self-efficacy; and grade motivation. The research indicates exposures to learning modules did not contribute to any significant gender disparity and both genders improved motivations to learn nanoscience after participating in the learning module. The main implications of this study were providing students with computer-based handson and computer-simulated learning experiences in a contemporary nanoscience area as well as highlighting opportunities for a more authentic process of inquiry-based learning in nanoscience education.