Heart failure (HF) is a leading cause of mortality worldwide. The pathogenesis of HF is complex and has not yet been fully elucidated, which has slowed drug development and long-term treatments. Inflammasome-mediated responses occur during the progression of HF. It has been reported that energy metabolism and metabolites of intestinal flora are also involved in the process of HF, and they interact with each other to promote the progression of HF. NLR family pyrin domain containing 3 (NLRP3) inflammasome may be a key target in the relationship between inflammation-mediated energy metabolism and metabolites of intestinal flora. Elucidating the relationship among the above three factors may help to identify new molecular targets for the prevention and treatment of HF and ultimately affect the course of HF. In this study, we systematically summarize evidence regarding the relationship among NLRP3 inflammasome, energy metabolism, intestinal microflora metabolites, and inflammation, as well as highlight advantages of NLRP3 inflammasome in treating HF.