The advent of the COVID-19 vaccine signified a historic milestone in the field of vaccinology, showcasing remarkable scientific collaboration and global solidarity. However, the most prominent hurdle in maximizing the global public health impact of vaccines remains the absence of comprehensive and inclusive health systems in both high- and low-resource settings. Our discussion centers around the major contributing factors that played a key role in formulating the rapid and efficacious COVID-19 vaccines. Simultaneously, we illuminate the disparities that have marred the vaccine delivery process throughout the pandemic. In particular, we highlight the case scenarios of two minority and vulnerable communities from the Global South and North—the undocumented migrants in Thailand and the Roma community in Europe—who continue to experience inequitable vaccine access regardless of their location. We note that a crucial programmatic solution that is rooted in inclusive and equitable global public health policy, characterized by empathy and trust and bolstered by digital innovation, is lacking. These examples underscore the significance of establishing a comprehensive and integrated health system at multiple levels across countries and the entire world. Furthermore, we highlight the need for both local and global actors to collaboratively engage in vaccine distribution efforts. By gaining a concise grasp of these intricacies, the global community will be better poised to effectively combat future pandemics and emerging health challenges.