Covid-19 pandemic has changed daily life in the city of Athens where vaccines are exploited with supply chain technology potentiality. Vaccines are tracked at the city’s airport till their delivery to vaccination centers. Due to the sensitivity of vaccines to the warm climate inherent in the city, delivery is assigned to a fleet of trucks. Specifically, two use cases, i.e., UC-I and UC-II, are proposed, which are based on global and local routing algorithms to exploit trucks’ load COVID-19 vaccine delivery from the airport and transport it to vaccination centers. In this paper, we focus on the supply chain routing algorithm technology of collecting COVID-19 vaccines from the airport and delivering them to vaccination centers in the smart city of Athens, Greece. Concretely, the purpose and the objectives of the research effort are in the areas of: (1) describing in deep detail the proposed supply chain system, (2) exploiting the adopted architecture based on certain separate use cases for system experimentation, (3) adopting specific vaccination routing algorithms to support vaccination distribution, and (4) evaluating experimentally the proposed supply chain system architecture with regards to the adopted use cases’ routing algorithms.