Abstract Introduction In epidemiology, establishing causation requires meeting rigorous criteria beyond mere association. Traditional methodologies often struggle to provide definitive causal conclusions due to confounding variables. However, leveraging artificial Intelligence (AI) and machine Learning (ML) offers a promising solution by modeling complex interactions among relevant factors. This systematic review explores the AI techniques utilized to uncover causal relationships in public health applications. Methods A literature search was conducted in Pubmed, Web of Science, and Scopus, employing the following search strategy: (Causalit*[Title/abstract] OR Causation*[Title/abstract] OR Causal[Title/abstract]) AND (‘Machine Learning’[Title/abstract] OR “Deep Learning” [Title/abstract] OR ‘Artificial Intelligence’ [Title/abstract] OR Algorithm* [Title/abstract]). The search aimed to identify studies encompassing causal inference techniques utilizing ML and AI methodologies in public health. Results From a total of 28,230 articles published up to August 2023, after removing duplicates (11,158) and articles that did not meet the inclusion criteria (16,168 post title/abstract screening, and 856 post full-text screening), the systematic review included 48 articles. Bayesian additive regression trees, Bayesian network models, causal forests analysis, and graphical causal models emerged as the prevailing causal methodologies. AI-driven causal methodologies have been investigated across various domains within public health, encompassing disease prediction, evaluation of treatment efficacy, identification of risk factors, analysis of health behaviors, precision Public Health initiatives, and environmental health assessment. Discussion While our systematic review affirms the potential of AI-driven causal approaches across several public health domains, further research is warranted before these emerging techniques can be effectively integrated into real settings. Key messages • In epidemiology, establishing causation requires meeting rigorous criteria beyond mere association and traditional methodologies often struggle to provide definitive causal conclusions. • This systematic review explores the AI techniques utilized to uncover causal relationships in public health applications.