The current study investigated the cognitive deficit profiles among individuals with mathematics difficulties (MD) and potential moderators and mechanism for these profiles. Seventy-five cognitive profiling studies on MD were included, representing a total of 13,001 individuals and 126 independent samples. Results showed that compared with typically developing individuals, individuals with MD showed deficits (from most severe to less severe) in phonological processing, processing speed, working memory, attention, short-term memory, executive functions, and visuospatial skills. Moderation analyses indicated that comorbidity (with reading disabilities) and types of MD screening affected the cognitive deficits. Severity of MD was related to processing speed deficits. Deficits in phonological processing and attention were more severe in younger individuals with MD. Deficits in processing speed and working memory were most severe in the numerical domain. Deficits in low-level cognitive skills (i.e., processing speed and short-term memory) could not completely explain the deficits in high-level skills (i.e., working memory, attention, and executive functions), partially supporting the bottleneck theory. These findings, taken together, suggest that (a) deficits in processing speed and working memory are most salient and stable cognitive markers of MD, (b) numerical-processing deficit and the cognitive deficits of MD are relatively independent from each other, and (c) MD may be a discrete construct with heterogeneity reflected by MD subtypes and age. Implications for incorporating cognition in the diagnosis and the interventions for MD are discussed.