Background Exploring the association of coronavirus-2019 disease ( COVID-19 MESHD) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic to optimize survival. The objective of this systematic review and meta-analysis is to explore the association of pre-existing conditions with COVID-19 MESHD mortality. Methods We searched MEDLINE, OVID databases, SCOPUS, and medrxiv.org for the period December 1, 2019, to May 1 HGNC, 2020. The outcome of interest was the risk of COVID-19 MESHD mortality in patients with and without pre-existing conditions. Comorbidities explored were cardiovascular diseases MESHD ( coronary artery disease MESHD, hypertension MESHD, cardiac arrhythmias MESHD, and congestive heart failure MESHD), chronic obstructive pulmonary disease MESHD, type 2 diabetes MESHD, cancer MESHD, chronic kidney disease MESHD, chronic liver disease MESHD, and stroke MESHD. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Results Ten chronic conditions from 19 studies were included in the meta-analysis (n = 61,455 patients with COVID-19 MESHD; mean age, 61 years; 57% male). Overall the between-study study heterogeneity was medium and studies had low publication bias MESHD and high quality. Coronary heart disease MESHD, hypertension MESHD, congestive heart failure MESHD, and cancer MESHD significantly increased the risk of mortality from COVID-19 MESHD. The risk of mortality from COVID-19 MESHD in patients with coronary heart disease MESHD was 2.4 times as high as those without coronary heart disease MESHD (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension MESHD as high as that compared to those without hypertension MESHD (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer MESHD also were at twice the risk of mortality from COVID-19 MESHD compared to those without cancer MESHD (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure MESHD were at 2.5 times the risk of mortality compared to those without congestive heart failure MESHD (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions COVID-19 MESHD patients with all any cardiovascular disease MESHD, coronary heart disease MESHD, hypertension MESHD, congestive heart failure MESHD, and cancer MESHD have an increased risk of mortality. Tailored infection MESHD prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.