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Abstract Background Individuals with severe mental illness, e.g. schizophrenia have up to a 20% shortened life expectancy compared to the general population. Cardiovascular disease, due to cardiometabolic risk and metabolic syndrome, accounts for most of this excess mortality. A scoping search revealed that there has not been a review of published studies on the role of pharmacy in relation to cardiometabolic risk, metabolic syndrome and related diseases (e.g. type 2 diabetes) in individuals with severe mental illness. Methods A mixed-methods systematic review was performed. Eleven databases were searched using a comprehensive search strategy to identify English-language studies where pharmacy was involved in an intervention for cardiometabolic risk, metabolic syndrome or related diseases in severe mental illness in any study setting from any country of origin. First, a mapping review was conducted. Then, implementation strategies used to implement the study intervention were classified using the Cochrane Effective Practice and Organisation of Care Taxonomy. Impact of the study intervention on the process (e.g. rate of diagnosis of metabolic syndrome) and clinical (e.g. diabetic control) outcomes were analysed where possible (statistical tests of significance obtained for quantitative outcome parameters reported). Quality assessment was undertaken using a modified Mixed Methods Appraisal Tool. Results A total of 33 studies were identified. Studies were heterogeneous for all characteristics. A total of 20 studies reported quantitative outcome data that allowed for detailed analysis of the impact of the study intervention. The relationship between the total number of implementation strategies used and impact on outcomes measured is unclear. Inclusion of face-to-face interaction in implementation of interventions appears to be important in having a statistically significantly positive impact on measured outcomes even when used on its own. Few studies included pharmacy staff in community or general practitioner practices (n = 2), clinical outcomes, follow up of individuals after implementation of interventions (n = 3). No studies included synthesis of qualitative data. Conclusions Our findings indicate that implementation strategies involving face-to-face interaction of pharmacists with other members of the multidisciplinary team can improve process outcomes when used as the sole strategy. Further work is needed on clinical outcomes (e.g. cardiovascular risk reduction), role of community pharmacy and qualitative studies. Systematic review registration PROSPERO CRD42018086411