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The vast potential of human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) in preclinical models of cardiac pathologies, precision medicine, and drug screening remains to be fully realized because hiPSC-CMs are immature without adult-like characteristics. Here, we present a method to accelerate hiPSC-CM maturation on a substrate, cardiac mimetic matrix (CMM), mimicking adult human heart matrix ligand chemistry, rigidity, and submicron ultrastructure, which synergistically mature hiPSC-CMs rapidly within 30 days. hiPSC-CMs matured on CMM exhibit systemic transcriptomic maturation toward an adult heart state, are aligned with high strain energy, metabolically rely on oxidative phosphorylation and fatty acid oxidation, and display enhanced redox handling capability, efficient calcium handling, and electrophysiological features of ventricular myocytes. Endothelin-1-induced pathological hypertrophy is mitigated on CMM, highlighting the role of a native cardiac microenvironment in withstanding hypertrophy progression. CMM is a convenient model for accelerated development of ventricular myocytes manifesting highly specialized cardiac-specific functions. [Display omitted] • Rapid iPSC-CM maturation on surfaces mimicking native cardiac microenvironment • Concurrent metabolic and redox maturation on cardiac mimetic matrix (CMM) • Hybrid Steiner tree network identifies intermediaries involved in cardiac maturation • Cardiac ultrastructure moderates hypertrophic disease phenotype Afzal et al. induce physiologically inspired cardiac maturation. The resulting cardiac constructs display features of ventricular myocytes within 30 days including structural alignment, electrophysiological maturation, molecular signature, mitochondrial energetics and fatty acid oxidation, and efficient oxidative stress handling capability, facilitating their use in disease modeling and preclinical drug screening. [ABSTRACT FROM AUTHOR]