This study reports the development of a highly absorbent Chitosan (CS)/Tannic Acid (TA) sponge, synthesized via chemical cross-linking with Epichlorohydrin (ECH) and integrated with zinc oxide nanoparticles (ZnO NPs) as a novel hemostatic anti-infection agent. The chemical properties of the sponges were characterized using Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and zeta potential measurements. Morphological and elemental analyses conducted through scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX) revealed a uniform distribution of ZnO NPs, with particle sizes below 20 nm. Compression tests indicated that the incorporation of ECH enhanced the compressive strength of the TA/CS sample, increasing from 0.614 MPa to 1.03 MPa for TA/CS-ECH and 1.16 MPa for ZnO@TA/CS-ECH, while preserving its flexibility. ZnO@TA/CS-ECH sponges exhibited high swelling ratios, consistent with their mesoporous structure revealed by porosity analysis. MTT assays confirmed that the addition of ECH did not adversely affect the biocompatibility of the final ZnO@TA/CS-ECH sample. Hemostatic performance was assessed through prothrombin time (PT), activated partial thromboplastin time (aPTT), blood clotting index (BCI), blood clotting time (BCT) assays, and platelet adhesion imaging. ZnO@TA/CS-ECH significantly reduced the BCT of untreated blood from 349 to 49 s, outperforming Celox™ (182 s). This performance was further confirmed using a rat liver hemostatic model. Moreover, ZnO@TA/CS-ECH demonstrated substantial antimicrobial activity against E. coli, S. aureus, and C. albicans, comparable to standard antibiotics and antifungals. These findings suggest that the three-dimensional ZnO@TA/CS-ECH sponge holds promise in managing infected bleeding and inspiring the next-generation of hemostatic agents.