Multiple interconnected molecular pathways govern cardiac hypertrophy, including PI3K-Akt-mTOR, MAPK signaling, and AMPK regulation, but emerging evidence highlights the gut-heart axis as a previously underappreciated systemic regulator of cardiac remodeling. This represents a fundamental shift from viewing heart failure as purely a cardiac phenomenon to understanding it as part of a broader metabolic and microbial ecosystem. The gut microbiota's influence on cardiac hypertrophy opens entirely new therapeutic avenues beyond traditional cardiovascular interventions. Targeting microbial composition or metabolites could potentially prevent the transition from adaptive cardiac hypertrophy to maladaptive heart failure. However, this review reveals critical knowledge gaps in mechanistic specificity and early detection methods. The complexity of overlapping signaling networks—from transcriptional control to mitochondrial dynamics—suggests that single-target therapies may prove insufficient. The field appears poised for a paradigm shift toward multi-omics approaches that integrate metabolic, epigenetic, and microbial data. This holistic perspective could revolutionize prevention strategies, moving from reactive cardiac interventions to proactive ecosystem management that maintains cardiac health through systemic regulation.