<p>High-quality interactions between child-care professionals and children are central to early development. Despite extensive research and policy interest, no prior review has integrated evidence across the broad set of factors linked to interactive skills of individual caregivers in early childhood education and care (ECEC). This preregistered systematic review and meta-analysis examined factors associated with observer-rated interactive skills of child-care professionals in formal ECEC settings for children up to 6.0 years. A systematic search was conducted across five databases (ERIC, PsycINFO, PubMed, SocINDEX, Web of Science), and study quality was assessed using the Appraisal Tool for Cross-Sectional Studies. A three-level random effects model was applied to estimate effect sizes. Across 57 eligible studies, 70 factors associated with caregiver interactive skills were identified; 41 studies contributed data for meta-analysis, yielding 13 factors for quantitative synthesis. Structural factors significantly associated with higher levels of interactive skills included higher caregiver education (<i>r</i> = .21), smaller group sizes (<i>r</i> = − .20), lower child-caregiver ratios (<i>r</i> = − .13), and higher salaries (<i>r</i> = .22). Individual factors associated with higher levels of interactive skills included mentalizing abilities (<i>r</i> = .17) and mental well-being (<i>r</i> = .08). Work experience, tenure, perceived support, stability, caregiver age, child sex, and center size showed no significant associations. Policies and interventions that both address structural conditions and support caregivers’ well-being and psychological resources are most likely to enhance interaction quality and, ultimately, children’s developmental outcomes.</p>