In this synthesis, we reviewed 65 studies involving elementary students (i.e., grades 1–5) identified with mathematics difficulty (MD) in which authors implemented a mathematics intervention. Of these studies, we identified 33 group designs, 9 quasi-experimental designs, and 23 single-case designs. We aimed to synthesize performance differences between students with MD with and without reading difficulty (RD). We identified three categories of students for analysis: Students with MD+RD, MD-alone, or MD-nonspecified (i.e., no reading information provided). Overall, 80% of studies included students with MD-nonspecified, and the interventions for these students demonstrated strong effects. For the limited number of studies with students with MD+RD or MD-alone, intervention effects were strong for students with MD+RD and variable for students with MD-alone. In the three studies directly comparing the performance of students with MD+RD versus MD-alone, we noted differential patterns of performance. To tailor interventions to student need, more research must be conducted to understand whether students with MD with variable reading profiles respond differentially to mathematics intervention.