Efforts are ongoing to enhance the functionality of human acellular dermal matrices (hADMs), which are extensively utilized in reconstructive surgeries. Among these efforts, plasma treatments, particularly vacuum plasma treatments, have recently emerged in the medical field. This study aims to investigate the efficacy of a vacuum plasma treatment in enhancing the biocompatibility and biointegration of hADMs. Utilizing a plasma activator (ACTILINK reborn, Plasmapp Co., Ltd., Daejeon, Republic of Korea), hADMs were treated and evaluated through in vitro and in vivo analyses. Hydrophilicity changes were gauged by the blood absorption times, while SEM imaging was used to analyze physical surface deformation. Protein adsorption was measured with fluorescently labeled bovine serum albumin and fibronectin. For the in vivo study, mice were implanted with plasma-treated and untreated hADMs, and the post-implantation effects were analyzed through histological and immunofluorescence microscopy. The plasma-treated hADMs demonstrated a significantly enhanced hydrophilicity compared to the untreated samples. SEM imaging confirmed the maintenance of the microroughness after the treatment. The treated hADMs showed a significant reduction in fibronectin adsorption, a critical factor for cellular adhesion. In vivo, the plasma-treated hADMs exhibited reduced capsule formation and enhanced fibroblast infiltration, indicating improved biocompatibility and integration. These findings highlight the potential of a plasma treatment to enhance the performance of hADMs in clinical settings, offering a promising avenue for improving reconstructive surgery outcomes.