To identify the current literature regarding healthcare resource use and cost burden of asthma in the US. EMBASE® and MEDLINE® were systematically searched for 2015–2019 to identify English-language articles reporting the clinical and economic burden of asthma in the US. Two reviewers independently screened citations and extracted data. Of 951 citations screened, 91 publications met the inclusion criteria. The total cost of asthma in 2013 (inflated to 2015; data from Medical Expenditure Panel Survey) was $81.9 billion including costs due to absenteeism ($50.3 billion), losses due to missed work/school days ($3 billion), and mortality ($29 billion). Between 2008 and 2013, the annual per-person incremental medical cost of asthma was $3,266 (Nurmagambetov 2018). For school-aged children (SAC), the total annual healthcare expenditures attributable to asthma in 2013 (inflated to 2015) was $5.92 billion (Sullivan 2017). The latest data are inflated to 2015 in studies; however, the medical inflation rates in the US between 2015 and 2020 do not drastically impact the costs reported for overall burden. During 2007–2013, SAC with asthma/their caregivers missed 1.54/1.16 times the number of school days/number of workdays to care than those without asthma (Sullivan 2018). Among all asthma emergency department visits recorded in the National Hospital Ambulatory Medical Care Survey during 2002–2012, 12.3% resulted in hospitalization and 1.0% resulted in critical care unit transfer (Caspard 2017). A study on subsequent hospital readmission rates where asthma was the primary diagnosis within 30 days following an original asthma admission through the years 2009–2013 found these to be 5.1%, 5.4%, 5.3%, 5.1% and 5.1%, respectively (Obaidat 2016). The identified evidence shows that despite all efforts, asthma continues to be a significant burden to children, adults, and their caregivers. No recent costs related to burden of asthma have been identified, indicating an unmet need.