Abstract: The main objective of this study is to propose the conceptual framework for the integration of 21st century skills in biology education in Malaysia. An interdisciplinary approach for Biology, Technology, Engineering and Mathematics (BTEM) is suggested to imbibe 21st century skills into the existing Biology curriculum. Solving complex and interdisciplinary worldwide biology problems will require students to understand what connections exist across disciplines and how to make those connections. BTEM allows students to master biological knowledge and at the same time to be adroit in other sub disciplinary skills. The main teaching and learning strategies that apply in the BTEM subjects are problem-based learning and inquiry-based learning which require the coordination of both knowledge and skills simultaneously. This is intended to enhance the students’ abilities to construct their own knowledge through the relevant hands-on and minds-on activities. The essence of engineering is production of design for the inventive problem solving. Integrating advanced information communication technologies such as e-tools and World Wide Web resources are believed to be able to fulfil the learning style needs of the current ‘Net Generation’. Mathematics plays an important role providing computational tools for biology and engineering, especially in analysing data. The expected outcomes of BTEM implementation are the inculcation of 21st century skills digital literacy, inventive thinking, effective communication, high productivity, spiritual and noble values in Malaysian students.