To combat the COVID-19 pandemic, the scientific community has progressed from discovering antivirals to the large-scale production of vaccines. Mass vaccination programs to curb the COVID-19 pandemic started in many parts of the world at the beginning of 2021. Mass vaccination aims to exit from health emergencies by vaccinating all the population with the required dose in the shortest possible time. The production rate has been boosted, and many new production facilities have been opened to fulfill worldwide demand. The objective of the vaccination program is to maximize the medical benefit with the lowest cost and equitable distribution of vaccines worldwide. However, the environmental impact of this long-run immunization program has received very little attention. This study explores the environmental impact of the vaccine supply chain (VSC) and analyzes the mitigation strategies to minimize it without affecting the medical, economic, and social benefits of vaccination. The fuzzy DEMATEL technique has been used to prioritize the mitigation techniques and find cause and effect relations among them. The finding of studies shows that the “optimal vial design” is most important, and “vaccine awareness and education” is the most impactful strategy to tackle the environmental impact of VSC.