Nursing is an essential part of our health care system workforce. Cardiovascular and stroke nursing represents one of the largest specialty areas requiring expert knowledge and clinical proficiency to ensure safety and quality patient outcomes. To support the growth and sustainability of the various nursing roles in clinical practice, academia, and research, it is vital to attract, engage, mentor, and retain nurses. However, as the health care needs of the nation rise, staff nurses, advanced practice registered nurses, nursing educators, and nurse scientists are experiencing unprecedented demands, and individual wellness and burnout are being more closely examined at both the university and health care system levels. The goal of this scientific statement is to outline the drivers of burnout or intent to leave the profession that impact wellness specific to academic and clinical cardiovascular and stroke nursing and propose system-level interventions to mitigate and support future and current nurse clinicians, nurse educators, and nurse scientists.