Single-atom catalysts (SACs) have been extensively studied for their maximized atom availability, excellent catalytic activity, and high selectivity. With the surging research on SACs, the potential candidates of central atom sites have expanded beyond the well-studied transition metal elements. Among them, the emerging SACs based on the main group elements and lanthanide families possess unique electronic energy levels that significantly differ from the d-band electronic structures in transition metal-based SACs. These advantages enable them to exhibit significant potential in catalysing specific reactions and improving our understanding of reaction mechanisms in single-atom catalysis. This review provides a comprehensive overview of the latest advances in SACs based on the main group elements and lanthanide series metals, focusing on their synthetic strategies, the inherent single-atomic site-support interactions, and their applications in various catalytic reactions. Finally, future research perspectives and challenges regarding the way forward for main group elements and lanthanide series-based SACs have been outlined.