Background The rapid development of COVID-19 vaccines highlighted the transformative potential of artificial intelligence (AI) in modern vaccinology, accelerating timelines from years to months. Nevertheless, the specific roles and effectiveness of AI in accelerating and enhancing vaccine research, development, distribution, and acceptance remain dispersed across various reviews, underscoring the need for a unified synthesis. Methods We conducted an umbrella review to consolidate evidence on AI’s contributions to vaccine discovery, optimization, clinical testing, supply-chain logistics, and public acceptance. Five databases were systematically searched up to January 2025 for systematic, scoping, narrative, and rapid reviews, as well as meta-analyses explicitly focusing on AI in vaccine contexts. Quality assessments were performed using the ROBIS and AMSTAR 2 tools to evaluate risk of bias and methodological rigor. Results Among the 27 reviews, traditional machine learning approaches—random forests, support vector machines, gradient boosting, and logistic regression—dominated tasks from antigen discovery and epitope prediction to supply‑chain optimization. Deep learning architectures, including convolutional and recurrent neural networks, generative adversarial networks, and variational autoencoders, proved instrumental in multiepitope vaccine design and adaptive clinical trial simulations. AI‑driven multi‑omic integration accelerated epitope mapping, shrinking discovery timelines by months, while predictive analytics optimized manufacturing workflows and supply‑chain operations (including temperature‑controlled, “cold‑chain” logistics). Sentiment analysis and conversational AI tools demonstrated promising capabilities for real‑time monitoring of public attitudes and tailored communication to address vaccine hesitancy. Nonetheless, persistent challenges emerged—data heterogeneity, algorithmic bias, limited regulatory frameworks, and ethical concerns over transparency and equity. Discussion and implications These findings illustrate AI’s transformative potential across the vaccine lifecycle but underscore that translating promise into practice demands five targeted action areas: robust data governance and multi‑omics consortia to harmonize and share high‑quality datasets; comprehensive regulatory and ethical frameworks featuring transparent model explainability, standardized performance metrics, and interdisciplinary ethics committees for ongoing oversight; the adoption of adaptive trial designs and manufacturing simulations that enable real‑time safety monitoring and in silico process modeling; AI‑enhanced public engagement strategies—such as routinely audited chatbots, real‑time sentiment dashboards, and culturally tailored messaging—to mitigate vaccine hesitancy; and a concerted focus on global equity and pandemic preparedness through capacity building, digital infrastructure expansion, routine bias audits, and sustained funding in low‑resource settings. Conclusion This umbrella review confirms AI’s pivotal role in accelerating vaccine development, enhancing efficacy and safety, and bolstering public acceptance. Realizing these benefits requires not only investments in infrastructure and stakeholder engagement but also transparent model documentation, interdisciplinary ethics oversight, and routine algorithmic bias audits. Moreover, bridging the gap from in silico promise to real‑world impact demands large‑scale validation studies and methods that can accommodate heterogeneous evidence, ensuring AI‑driven innovations deliver equitable global health outcomes and reinforce pandemic preparedness.