Introduction In healthcare, just like in many other occupational fields, burnout is a health and well-being draining phenomenon that manifests in the form of chronic workplace stress, exhaustion or energy depletion, cynicism, elevated mental dissociation, and disengagement from activities that one would normally do (The World Health Organization [WHO], 2019). In the United States, burnout affects about 40% of doctors and nearly half of all nurses (Wan, 2019). However, it is important to note that the burnout problem does not only affect the doctors and nurses. Other specialties within the healthcare field are equally or probably more affected by burnout, as has been reported among neurosurgeons (Shakir et al., 2018), residents, and pharmacists (El-Ibiary et al., 2017) Purpose The purpose of this study was to conduct a systematic review of published literature from 2005 through 2021 to understand burnout among various categories of healthcare workers in the US before and during the COVID-19 pandemic and to explore and identify strategies to mitigate the impact of the burnout problem. Relevant studies were identified from various databases using combinations of relevant keywords. Results The review included 21 studies for final synthesis. Results from these studies demonstrated a gradual trend of increase in burnout before the COVID-19 pandemic, but the increase was drastic after the onset of the pandemic. For instance, before the pandemic, the lowest rate of burnout was reported at 13.5% among perfusionists, and the highest was reported at 51.78% found among physicians. However, when the COVID-19 pandemic started, this changed to the lowest rate reported at 42% among critical care physicians and the highest, 84.1% reported among pathologists and laboratory professionals. The rise in burnout was linked to increased workload following a high demand for care services by COVID-19 patients. A surge in COVID-19 infections directly translated to high patient-healthcare worker engagement, which proved to have a negative bearing on healthcare workers' effectiveness and well-being. Burnout causes many healthcare workers to abandon their work and employment, mostly so due to anxiety and fears of contracting COVID-19 and lack of reliable protective equipment, leading to severe staff shortages. As reported by Rodriguez et al. (2020), many healthcare organizations in the United States cannot effectively retain their healthcare professionals because they readily quit their employment due to burnout. It is also important to note that different categories of healthcare professionals experience different levels of burnout. Those who have signs of burnout but still work are faced with challenges of diminished interest in their work, are less productive, and prone to making errors, and collectively these are grounds for poor service delivery and harm to patients. To address burnout and its effects and impacts among healthcare workers in the United States, many evidence-based strategies are increasingly being applied. Evidence-based practice requires that an issue be identified and research that has been proven and tested be used to address the problem and ensure improved patient care and outcomes. Conclusions Findings from this systematic review are a good addition to the already existing body of reviews, including data on the presence of burnout among various categories of healthcare workers in the US before and during the COVID-19 pandemic. This review also underscores the need to promote the use of evidence-based strategies to mitigate burnout and its effects and outlines examples of some of these strategies.