To address the need for STEM reform in K-12 schools, this article describes the design and implementation of a rigorous, interdisciplinary science and research program (ISR) in two local high schools (HS-S and HS-H). The ISR, adapted from the successful School for Science and Math at Vanderbilt program, provides seven courses over four years that focus on the development of critical thinking skills and the ability to construct and perform hypothesis-driven research projects. The courses are co-taught by a science teacher (masters or doctoral level) and a Ph.D. scientist. Overall, students in both programs showed higher science end-of-course test scores and ACT composite scores compared to their non-ISR peers, completed research internships at Vanderbilt, and presented their research at local and regional meetings. Currently 62 of the 77 ISR graduates are attending college, with 62% of the declared majors in STEM areas. As the programs have matured, challenges such as low student preparation (ISR-S) and competition with other school academic offerings (ISR-H) have been addressed, resulting in increased numbers of students participating in the program. The school district has demonstrated the value of the ISR program by providing funding for the scientists and expanding to a third school in 2016.