BACKGROUND: Despite the public acceptance of COVID-19 vaccines being necessary to achieve ample immunization rates and, in turn, put an end to the global pandemic, vaccine hesitancy and refusal are on the rise. To detect and address the concerns of those who are hesitant, it is critical to identify all potential factors behind vaccine decision-making in order to devise strategies to enhance vaccine acceptance and uptake. METHODS: We retrieved a total of 742 and 685 completed questionnaires from Iran and France, respectively; after initial cleaning and data screening, the number of usable questionnaires dropped to 714 and 664. We evaluate the distinct vaccination and lockdown restrictions in Iran and France and used multi-group analysis to evaluate structural path models of French and Iranian people, revealing a significant difference between the two groups in vaccination-related decisions. This empirical study is one of the first to employ the measurement invariance was evaluated using the measurement invariance for composite (MICOM) approach in testing partial least squares-structural equation modelling (PLS-SEM) measurement invariance and one of the first to use both Henseler's MGA and Henseler's permutation method to perform multi-group analysis (MGA). RESULTS: MGA revealed significant differences in the effects of influential factors on vaccine acceptance across France and Iran. In other words, many determining factors are likely to be context-dependent. The study revealed that reactance (due to restrictions and perceived scarcity) and financial strain significantly influenced COVID-19 vaccine acceptance and uptake among Iranians; however, among the French, confidence, and convenience were far more influential. CONCLUSIONS: These cross-cultural differences point to the importance of conducting additional research in this area that directly compares various effects across countries. Each country's public health authorities and policymakers could use these insights to develop more targeted strategies and, in turn, boost vaccination rates among the public.