Burnout among palliative care (PC) providers has been extensively documented, yet little is known about the experiences of inpatient, hospital-based PC nurse practitioners (NPs). This dissertation presents a cohesive body of work that explores and conceptualizes burnout among this population. Guided by Lazarus and Folkman’s cognitive appraisal theory (CAT), the study examined how NPs’ appraisals of stress and coping interact with the high-intensity hospital environment of palliative care. The first manuscript, a systematic literature review, examined what is known about burnout among PC providers. Findings revealed that while burnout prevalence among PC providers is concerning across palliative disciplines, few studies focused specifically on NPs or distinguished the inpatient setting from outpatient or hospice contexts. Depersonalization (DP), a core dimension of burnout, emerged as a particularly concerning aspect among clinicians. The second manuscript critically evaluated the psychometric properties of existing burnout instruments, especially those that measure DP. Results demonstrated that no instrument adequately captures the unique experience of burnout among inpatient, hospital-based PC NPs, thereby limiting their utility in guiding intervention research. Together, these manuscripts identified significant knowledge gaps that informed the third manuscript: a qualitative descriptive study exploring the firsthand experiences of inpatient hospital-based PC NPs. Eligible participants were U.S.-based NPs aged 18 years or older, working in inpatient PC for at least one year. Data were collected through audio- and video-recorded semistructured interviews, transcribed verbatim, and analyzed using inductive content analysis. Twenty-one participants were recruited through purposive sampling. All participants practiced in urban hospitals (N = 21), were female (n = 19) and male (n = 2), identified as White (n = 20) or Mexican American (n = 1), and had 1–15 years of inpatient PC NP experience. Findings revealed that burnout is shaped by moral tension, emotional exhaustion, constrained autonomy, systemic and organizational barriers, and late consults that challenge the relational core of PC practice. Sustaining forces included professional role identity, autonomy, team cohesion, and patient connections. Within the context of limited organizational support, participants’ appraisal of their professional commitment underscored their susceptibility to exploitation. The synthesis of findings culminated in the development of the Concentric Ring Model of Stress and Coping, a visual framework illustrating the multilayered and interconnected factors that influence NP well-being.