This meta-analysis examined the effectiveness of supplemental Tier-2 mathematics interventions for students with mathematics difficulties (MD). We reviewed 39 experimental and quasi-experimental studies that included 40 independent samples, with 61 treatment groups. Utilizing robust variance estimation (RVE), results revealed a treatment effect of 0.41. Mixed-effects meta-regression analyses revealed that Tier-2 interventions were moderated by intervention model type, group size, and type of measure. We present recommendations for future research and implementation of mathematics practices.