Heart failure with preserved ejection fraction (HFpEF) is a growing public health concern, with rising incidence alongside high morbidity and mortality. However, the pathophysiology of HFpEF is not yet fully understood. The association between HFpEF and the metabolic syndrome (MetS) suggests that dysregulated lipid metabolism could drive diastolic dysfunction and subsequent HFpEF. Herein we summarise recent advances regarding the pathogenesis of HFpEF in the context of MetS, with a focus on impaired lipid handling, myocardial lipid accumulation and subsequent lipotoxicity.