Coronavirus disease (COVID-19) caused an overwhelming healthcare, economic, social, and psychological impact on the world during 2020 and first part of 2021. Certain populations, especially those with Substance Use Disorders (SUD), were particularly vulnerable to contract the virus and also likely to suffer from a greater psychosocial and psychological burden. COVID-19 and addiction are two conditions on the verge of a collision, potentially causing a major public health threat. There is surge of addictive behaviors (both new and relapse), including use of alcohol, nicotine, and recreational drugs. This book chapter analyzed the bi-directional relationship between COVID-19 and SUD by leveraging descriptive summaries, advanced analytics, and machine learning approaches. The data sources included healthcare claims data set as well as state level alcohol consumption to help in investigating the bi-directional relationship between the two conditions. Results suggest that alcohol and nicotine use increased during the pandemic and that the profile of SUD patients included diagnoses and symptoms of COVID-19, depression and anxiety, as well as hypertensive conditions.