<p>Pressure ulcers can lead to acute infections, delayed healing, and cause discomfort to patients with mobility challenges. Although there have been tremendous developments in nanoparticle-based wound care, most investigations remain limited in their ability to address the challenges of pressure ulcers in translational research. The of this review discusses the pathology-driven techniques that uniquely integrate nanoparticle design with specific mechanisms for identifying the pathways in pressure ulcer management. This novelty of this review mainly relied on the diverse techniques and design strategy to contain the pressure ulcers along with various metallic, polymeric, lipid-based, and carbon nanoparticles (NPs) and hydrogel-based NPs systems. The metal NPs are highly effective at controlling infection and facilitating wound healing due to their antimicrobial and anti-biofilm properties. The polymer-based NPs allow sustained, site-specific drug delivery and improve anti-inflammatory responses and tissue regeneration, while lipid-based nanoparticles and carbon-based nanoparticles enhance the drug’s entry into the cell and further improve anti-inflammatory and angiogenesis effects. These findings highlight the potential of metallic NPs, particularly silver and gold formulations, demonstrated the broad-spectrum of antimicrobial and antibiofilm properties highly relevant to the infected wound microenvironment of pressure ulcers, while lipid nanoparticles offered a superior biocompatibility and versatile drug encapsulation capacity suitable for anti-inflammatory therapeutic delivery. The polymeric NPs, including PLGA and chitosan-based formulations, provided a controlled and sustained drug release with biodegradable properties that minimize local tissue toxicity, and hydrogel NPs present unique advantages through their tissue-mimicking mechanical properties. The NPs based hydrogels are effective, biocompatible, and cost-efficient wound care alternatives. However, clinical translation remains limited by insufficient long-term biocompatibility data, absence of standardized dosing protocols, and limited in vivo validation across ulcer severity stages. The pathology-aligned nanoparticle engineering is concluded to be a promising and rational strategy for personalized pressure ulcer management, with defined research priorities identified to accelerate clinical adoption.</p> Graphical Abstract <p></p>