Background <p>Soft hydrated polymer networks are widely used as model systems for studying the response of biological tissues subjected to high strain-rate loading. While inertial cavitation generates extreme localized deformation fields, the effect of repeated cavitation events on the surrounding material remains poorly understood.</p> Objective <p>This work investigates how repetitive cavitation modifies the microstructure and mechanical response of hydrogels with distinct network architectures.</p> Methods <p>Laser-induced cavitation experiments combined with high-speed imaging, confocal microscopy, and inertial microcavitation rheometry are performed on chemically crosslinked polyacrylamide, physically crosslinked gelatin, and fibrous collagen networks subjected to repeated cavitation events.</p> Results <p>The results show that the dominant material modification occurs during the first cavitation event, which generates a localized near-field region surrounding the bubble that governs subsequent bubble dynamics. Chemically crosslinked polyacrylamide exhibits localized anisotropic damage features consistent with irreversible bond rupture, whereas physically crosslinked gelatin displays more diffuse structural rearrangement associated with reversible network junctions. Collagen networks exhibit strongly heterogeneous responses governed by the interaction between the cavitation deformation field and the intrinsic fiber architecture.</p> Conclusions <p>These findings demonstrate that repetitive cavitation primarily probes a pre-modified material region created by the initial event and that the nature of this modification depends strongly on network topology.</p>