BACKGROUND: The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes. METHODS: On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality. RESULTS: A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM. The meta-analyses revealed that a 1 μg/m increase in PM was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO), ozone (O), sulphur dioxide (SO), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality. CONCLUSION: This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.