Metal and metal oxide nanocomposites are promising candidates for heterogeneous catalytic applications. In this regard, most of the metal oxide inner core volume remains as a dead volume, not participating in the catalysis, only the metal/metal oxide hetero-junctions available at the surfaces are involved in the catalysis. Herein, we report a novel strategy for the infiltration of gold nanoparticles into the inner core of 3D-porous Prussian blue/Fe2O3 hetero-microstructures (PBFHM-Au) beyond its outer surface to form an advanced heterogeneous catalyst for the environmental remediation applications. The porosity of the Prussian blue microstructures is thermally tuned for the infiltration of gold ion precursor into the inner core volume of Prussian blue/Fe2O3 hetero-microstructures to facilitate the galvanic displacement reaction between Fe and Au to enlarge the lattice shell and form Au nanoparticle 3D networks throughout the PBFHM. Notably, the resulting PBFHM-Au2 shows enhanced structural stability electron transfer kinetics and catalytic activity in comparison with the only surface-attached Au/Fe2O3 composite. The obtained PBFHM-Au2 catalyst demonstrates remarkable catalytic activity for Rhodamine-B dye degradation with rate constant (k = 3.47 × 10−2 s−1) and p-nitrophenol reduction reactions with rate constant (k = 1.199 × 10−1 s−1).