<p>Chronic and non-healing wounds pose persistent clinical challenges due to infection, inflammation, and impaired tissue regeneration. Nanoparticle-infused hydrogels have emerged as next-generation wound dressings, offering synergistic benefits by combining the moisture-retentive, biocompatible properties of hydrogels with the multifunctional therapeutic capabilities of nanoparticles. This review presents a comprehensive overview of recent advancements in the design and biomedical application of nanoparticle-integrated hydrogels, highlighting their roles in accelerating wound repair, preventing infection, and promoting tissue regeneration. Recent advancements include the incorporation of silver and zinc oxide nanoparticles to boost antimicrobial and anti-inflammatory responses, while gold and cerium oxide nanoparticles have been explored for their antioxidant and tissue-regenerative properties. Additionally, magnetic and stimuli-responsive nanoparticles are being developed to enable targeted drug delivery and smart therapeutic responses. These multifunctional hybrid systems have shown promising outcomes in preclinical models, including accelerated wound closure, decreased microbial burden, and enhanced cellular activity. While the potential of these advanced platforms is considerable, translational barriers such as nanoparticle toxicity, long-term biocompatibility, and regulatory compliance remain to be addressed. By critically analyzing current strategies and identifying future directions, this review underscores the transformative potential of nanoparticle-infused hydrogels in modern wound care and their promising trajectory from bench to bedside.</p>