In this systematic review, we explored mathematics interventions for middle school (Grades 6, 7, and 8) implemented with students who experienced difficulty in the area of mathematics, including students with an identified learning disability in mathematics. A total of 72 single-subject and group comparison studies met inclusion criteria, with 59 studies demonstrating positive effects on student-level mathematics outcomes. The majority of mathematics interventions focused on foundational, prealgebraic skills (e.g., operations and problem solving) related to algebraic reasoning. To understand the landscape of effective mathematics interventions and inform instruction within mathematics intervention, we identified six instructional components used with regularity within the effective studies. These components included explicit instruction, multiple representations, problem-solving instruction, mathematical language, mnemonics, and graphic organizers.