Objectives: The purpose of this study was to understand how specific evidence-based design strategies are related to aspects of nurse wellness. Background: Addressing burnout among the healthcare workforce is a system-level imperative. Nurses face continuous and dynamic physical and emotional demands in their role. Greater insight into the role of the physical environment can support efforts to promote nurse wellness. Methods: This exploratory qualitative study was conducted at new Parkland Hospital in Dallas, TX. We conducted five focus groups with nursing staff in July 2018. These sessions covered five topics related to nursing work in the facility which had been redesigned nearly 3 years earlier: (1) professional and social communication, (2) workflow and efficiency, (3) nurses’ tasks and documentation, (4) ability to care for patients, and (5) nurses’ overall health. We conducted a thematic analysis and first identified different aspects of wellness discussed by participants. Then, we examined how nurses related different design elements to different aspects of their wellness. Results: Participants included 63 nurses and nurse managers. They related environmental factors including facility size, break rooms, and decentralized workstations to social, emotional/spiritual, physical, intellectual, and occupational aspects of wellness. Conclusions: It is critical to inform and integrate nurses at all levels into planning, design, and activation of new healthcare environments in order to ensure the well-being of nurses and, therefore, their ability to effectively support patients.