The increasing challenge of multiple chronic diseases (multimorbidity) requires more evidence-based knowledge and effective practice. In order to better understand the existing evidence on multimorbidity, we performed a systematic review of systematic reviews on multimorbidity with pre-established search strategies and exclusion criteria by searching multiple databases and grey literature. Of 8006 articles found, 53 systematic reviews (including meta-analysis and qualitative research synthesis performed in some reviews) that stated multimorbidity as the main focus were included, with 79% published during 2013–2016. Existing evidence on definition, measurement, prevalence, risk factors, health outcomes, clinical practice and medication (polypharmacy), and intervention and management were identified and synthesised. There were three major definitions from three perspectives. Seven studies on prevalence reported a range from 3.5% to 100%. As six studies showed, depression, hypertension, diabetes, arthritis, asthma, and osteoarthritis were prone to be comorbid with other conditions. Four groups of risk factors and eight multimorbidity associated outcomes were explored by five and six studies, respectively. Nine studies evaluated interventions, which could be categorized into either organizational or patient-oriented, the effects of these interventions were varied. Self-management process, priority setting and decision making in multimorbidity were synthesised by evidence from 4 qualitative systematic reviews. We were unable to draw solid conclusions from this overview due to the heterogeneity in methodology and inconsistent findings among included reviews. As suggested by all included studies, there is a need for prospective research, especially longitudinal cohort studies and randomized control trials, to provide more definitive evidence on multimorbidity.