The purpose of this article is to introduce a comprehensive instructional model that takes into consideration three frameworks for designing instruction (Universal Design for Learning, Understanding by Design, and the 7E Learning Cycle) and incorporates Technological Pedagogical and Content Knowledge and Mindset (attitudes, beliefs, dispositions toward teaching and learning) that serves to advance STEM (Science, Technology, Engineering, and Mathematics) instruction with pre-service teachers. The proposed model will be used in teaching pre-service prek-12 teachers in the following courses: Mathematics Methods, Science Methods, Human Development and Learning Theory, and Classroom Management. It explores how the frameworks, TPaCK, and Mindset can be integrated to form a holistic and interdisciplinary model for designing instruction, particularly in STEM courses. Each framework has a different focus, which is discussed, along with how TPaCK and Mindset can influence how one uses the framework to design instruction. Among these frameworks, there exists a convergence of pedagogy, instructional design, planning, and strategic use of technology that provides an opportunity for a holistic, interdisciplinary approach to designing instruction that serves both teacher and student: teachers in becoming more effective instructors, and students in becoming more effective learners. A brief review of each framework, TPaCK and Mindset is included as well as the description of The Oswald-Gentile Model of Instruction, a holistic approach to designing instruction that takes into consideration both the learner and the teacher.