<p>Among students who have learning difficulties in mathematics and reading, co-occurring difficulties in both domains are highly prevalent. Research has shown that students with co-occurring mathematics and reading difficulties tend to have greater cognitive challenges than students who have difficulties with either mathematics or reading. It is plausible that these cognitive difficulties can influence the responsiveness to interventions. This systematic review with meta-analysis investigated the effects and characteristics of mathematics interventions in early elementary students (G1-G3) with co-occurring difficulties in mathematics and reading, as well as how these students had been identified in the included studies. Based on a comprehensive literature search, only nine studies (<i>k</i> = 1036) met the predefined inclusion criteria. The available evidence indicates a positive overall mean effect of mathematics interventions on mathematical outcomes for students with co-occurring mathematics and reading difficulties (<i>g</i> = 0.47 for the model with outliers; <i>g</i> = 0.52 for the model without outliers). However, this result should be interpreted with caution, given the heterogeneity of the evidence and the relatively small evidence base. The synthesis of intervention characteristics highlighted that effective mathematics interventions commonly included explicit instruction, which was classified as potentially relevant for low-performing students, as well as overall structure, repetition, and strategy learning, which were classified as potentially relevant to support executive function. Finally, findings revealed considerable variation in the cut-off criteria used to identify students with co-occurring mathematics and reading difficulties. Implications of the findings and directions for future research are discussed.</p>