Cardiovascular disease (CVD) is the leading cause of death globally. People living with type 2 diabetes mellitus (T2DM) have a three times higher risk of developing CVD, particularly heart failure with preserved ejection fraction (HFpEF), for which there is no treatment. The need for tangible interventions has led to investigations into a number of biomarkers associated with metabolic and vascular dysfunction that could be utilised for diagnostic and treatment purposes. This review discusses the importance and mechanisms of inflammatory and angiogenic biomarkers, which have shown the most potential in the pathogenesis and diagnosis of HFpEF in the presence of diabetes. In depth “in silico” analysis was also carried out to identify pathogenic pathways associated with HFpEF, both in the presence and absence of diabetes. The results identified mostly inflammatory pathways associated with HFpEF in the presence of diabetes, and a number of pathways related to angiogenesis, remodelling and metabolism. In addition, the results also identified inflammation, in the absence of diabetes. The shared and unique pathways identified in HFpEF in the presence and absence of diabetes, should be explored further in order to improve management and outcomes of people living with HFpEF.