The American Nurses Association’s (ANA) Code of Ethics establishes that nurses have a duty to protect and advocate for vulnerable patients. This dissertation is responsive to that call by probing deeply into a concept critical to helping individuals minimize vulnerability— self-efficacy. This work focuses on two particularly vulnerable groups: family caregivers of older adults with cognitive impairment and persons with complex health and psychosocial needs experiencing homelessness. Both groups routinely face significant socioeconomic challenges and stresses to their health and wellness and suffer higher mortality and morbidity rates than the general American public. This dissertation also examines two periods of transitions when these individuals are especially vulnerable. Also, congruent with one of the overarching objectives of Healthy People 2030, this work contributes to efforts that aim to reduce health disparities in these vulnerable groups. Chapter One establishes the critical nature of this research, charters specific aims for this dissertation, and highlights this work's strengths, weaknesses, and limitations. Chapter Two updates the concept analysis of self-efficacy among family caregivers of cognitively impaired older adults. Chapter Three builds on the concept analysis by examining the impact of the Transitional Care Model (TCM) on caregiver self-efficacy as caregivers’ loved ones with cognitive impairment transition from the hospital to home. This chapter also explores whether socioeconomic mediates the relationship between self-efficacy and the TCM. Chapter Four further explores the concept of self-efficacy in vulnerable populations by examining facilitators and barriers impacting self-efficacy for people experiencing homelessness adapting to an interim supportive housing program and transitioning into permanent housing. Finally, Chapter Five highlights this vital work's clinical and policy implications. This dissertation aims to help researchers, direct care providers, and policymakers understand better how to support vulnerable populations. And this dissertation will fortify a nursing career serving our society’s most vulnerable through public service.