In this study, we designed and successfully prepared all solid state 2D/3D/2D rGO/Fe2O3/g-C3N4 nanocomposite by embedding 3D Fe2O3 nanoparticles on 2D g-C3N4 nanosheets to for 3D/2D Fe2O3/g-C3N4 followed by the addition of 2D rGO nanosheets via a simple hydrothermal technique with the support of response surface methodology for the first time. The formation of this unique 2D/3D/2D heterojunction leads to generate several nanochannels in their interfacial contact for high-speed photoinduced charge transfer. The considerable enhancement in photoinduced charge transportation and migration efficiency resulted in significant visible-light-driven degradation of emerging pharmaceutical condemnations. The 3D/2D Fe2O3/g-C3N4 nanocomposite was optimized by various concentrations of Fe2O3 in g-C3N4, followed by the optimization of rGO concentration in 2D/3D/2D rGO/Fe2O3/g-C3N4 nanocomposite to obtain maximum degradation efficiency. We observed that the 3% of rGO in 4% Fe2O3/g-C3N4 nanocomposite exhibited superior photocatalytic ability, nearly 22 times and 16 times higher than pristine g-C3N4 nanosheets towards tetracycline and ciprofloxacin degradation, respectively. The synergistic effect between 2D/3D/2D g- rGO/Fe2O3/g-C3N4 nanocomposites and the photocatalytic mechanism was well studied through various characterization techniques like XRD, FTIR, SEM-EDX-mapping, HR-TEM, UV–vis DRS, PL, XPS and EPR. In addition, the 2D/3D/2D rGO/Fe2O3/g-C3N4 nanocomposite exhibits excellent recyclability and stability, establishing a promising application in environmental remediation. This research would provide a noteworthy platform for the extensive photocatalytic properties of 2D/3D/2D heterojunction nanocomposite system with enhanced charge migration and separation. © 2019 Elsevier B.V.