The adhesion at the concrete/epoxy interface is crucial to the reinforcement of carbon fiber-reinforced polymer (CFRP) sheets. The multiscale mechanism of adhesion, particularly under a hygrothermal environment, yet remains largely unclear. This paper combines molecular dynamics (MD) and synthesis experiments of a novel single-phase calcium silicate hydrate (C-S-H) and epoxy composite to investigate the combined effects of aggressive chemicals and temperature on the bonding properties. MD models were constructed under various conditions on C-S-H/epoxy composites, whose equilibrium configuration, dynamic property, bond connection, interfacial interaction energy, and mechanical properties were quantified. In addition, the experiments were carried out under different temperatures and humidity conditions to explore the macroscopic splitting tensile property of the composites and further validate the MD results. The MD results suggest that the Ca ions on the C-S-H surface are crucial to the adhesion by forming Ca−O and Ca−N bonds with epoxy. However, these bonds were reduced in the presence of water molecules, with a reduction also of the interfacial energy. The degradation effects are exacerbated by the presence of NaCl solution, as Na ions gather around the interfacial region of C-S-H/ epoxy, further accumulating water molecules by forming hydrated ion clusters. This process is accelerated by elevated temperature. The experiment results suggest that without the influence of NaCl solution, a moist C-S-H surface turns to gain a stronger bonding with epoxy when the curing temperature is higher (40, 60 °C). Meanwhile, the bonding properties of a dry C-S-H surface and epoxy are less sensitive to temperature. This work provides new insight into understanding the bonding mechanism on the C-S-H/epoxy interface and may benefit the engineering application of CFRP-concrete reinforcement.