The efficacy of mathematics interventions for students with mathematics difficulties is a critical concern in educational research, particularly in light of the increasing demand for effective instructional strategies. While previous meta-analyses have explored various aspects of mathematics interventions, our study uniquely focuses on a broad range of intervention characteristics and their impacts on students’ mathematics proficiency. This meta-analysis reviewed 223 reports comprising 286 studies, encompassing data from approximately 56,477 participants. We analyzed several intervention characteristics as potential moderators, including (1) grade level, (2) group size, (3) content area, and (4) dosage. We also examined study level characteristics, including (1) research design, (2) fidelity, (3) year of study, (4) type of measure, and (5) study quality. Our findings revealed significant variability in intervention effectiveness based on targeted content areas, with fraction interventions demonstrating a pronounced impact on the effectiveness of interventions for students with MD. The study also underscored the challenges in educational research, marked by heterogeneity in type of measure and study designs. This comprehensive analysis contributes to the field by providing nuanced insights into the effectiveness of mathematics interventions, aiding educators and policymakers in developing strategies that effectively address the diverse needs of students with MD in various educational settings.