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This qualitative case study reports on processes and outcomes of the National Science Foundation (NSF)-funded System-Wide Change for All Learners and Educators (SCALE) project at the California State University, Northridge (CSUN). It addresses a critical challenge in studying systemic reform in complex organizations: the lack of methodologies that incorporate technical, social, cultural, and cognitive elements. Guiding questions include (a) how the institutional context influenced the project, (b) whether project activities affected science, technology, engineering, and mathematics (STEM) instruction, interdisciplinary collaboration on preservice programs, and inter-institutional collaboration on in-service programs, and (c) if and how change initiatives are accepted and incorporated. In-depth interviews (N = 34), relevant documents, and observation data were collected in 2006 and 2007. Findings identified several factors that supported and several that inhibited achievement of SCALE goals. Supportive factors included reform efforts already underway at CSUN, an institutional mission emphasizing undergraduate education, an active social network of STEM educators, and faculty experienced with inquiry-based STEM instruction. Inhibiting factors included a heavy faculty and staff workload, a lack of pedagogical training for new faculty hires, a limited pipeline of preservice science majors, funding limitations, and a pervasive sentiment that scientific legitimacy is equated with basic research and not teaching expertise. Into this context, SCALE introduced two activities, including thirteen 5-day science professional development workshops for 270 Los Angeles Unified School District (LAUSD) personnel, and four 15-day math professional development workshops for 83 LAUSD personnel. The project’s success was limited by the absence of SCALE leaders at CSUN, and the subsequent lack of an explicit theory of institutional change for CSUN. Instead, SCALE engaged CSUN as primarily a site for its already existing math and science institutes, and largely ceded the effort at institutional transformation to chance and the extant reforms at CSUN. An enduring lesson from this study is that efforts to change the culture of teaching and learning in STEM departments should focus on illuminating and then shifting the pervasive cultural schema that faculty hold for teaching and learning. This analysis suggests that shaping the culture of an organization may require comprehensive efforts to change the structural, social, and symbolic milieu in which individuals operate, in addition to efforts to change the cognitive processes that constitute individuals’ habits of mind. To accomplish this, leaders are encouraged to (a) conduct regular institutional assessments prior to program planning, (b) design neutral spaces in which different groups may interact, (c) recruit a skilled culture-broker when working with interdisciplinary groups, (d) marshal existing resources and reform projects to collectively target key leverage points, and (e) focus on developing cohorts of STEM educators in specific departments. (Contains 5 figures and 3 tables.)