<p>Hemodialysis (HD) remains a vital treatment for patients with end-stage kidney disease, yet the characteristics of dialysis membranes significantly influence therapeutic outcomes. Membrane fouling, often caused by protein adherence, reduces toxin clearance and may lead to fluid and electrolyte imbalances. Recent studies have focused on modifying membrane chemistry to improve biocompatibility and reduce fouling. Although advancements have been made in understanding the biochemical and inflammatory responses during HD, the underlying molecular mechanisms, especially those involving epigenetic regulation remain incompletely understood. This review explores recent progress in HD treatment, with a specific emphasis on inflammation, gene expression, and epigenetic alterations. We examine how pro-inflammatory cytokines activate transcription factors that regulate gene expression and how genetic variability within inflammatory genes adds complexity to these pathways. In parallel, we assess emerging biocompatible membrane technologies designed to reduce adverse interactions with blood components, thereby enhancing patient safety and treatment efficiency. In addition, we discuss how genetic and epigenetic changes such as DNA mutations, methylation patterns, and histone modifications may influence patient responses to HD and contribute to complications, including mental health disorders such as depression. These insights support the development of personalized HD strategies tailored to the molecular and genetic profiles of individual patients. By integrating current findings from genetics, epigenetics, and gene expression studies, this review provides a comprehensive perspective on HD-related inflammation and molecular dysregulation. Our goal is to highlight key interconnections and identify critical knowledge gaps that must be addressed to improve long-term outcomes and quality of life for HD patients.</p>