The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing and prognosis remains poor, with a high risk of mortality or hospitalizations for worsening heart failure events. Apart from sodium-glucose cotransporter-2 inhibitors and diuretics, the management of HFpEF is nowadays based on the different aetiologies and cardiovascular or non-cardiovascular comorbidities. A great heterogeneity of clinical profiles has been described in HFpEF, with several recent studies focused on the identification of different HFpEF phenotypes. In this review, we summarize available evidence on phenotype profiling in HFpEF, describing the different phenotypes with the relative therapeutic implications, and reporting other specific clinical conditions relevant for HFpEF differential diagnosis.