The review discusses the challenges in developing diagnostics and treatments for neurodegenerative diseases (NDs) due to their multifactorial pathogenesis. It highlights the emergence of advanced in vitro systems, such as microfluidic chips and organoid-on-a-chip models, which recapitulate patient-like pathophysiology and offer valuable insights for biomedical research and drug development. The review covers the interconnected pathogenic features of different NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). It details the specific pathogenic mechanisms in each disease, such as amyloid-β and tau protein dysfunction, neuroinflammation, mitochondrial dysfunction, and genetic alterations. The review also explores the limitations of current experimental models, particularly animal models, and emphasizes the advantages of microfluidic chips and organoids in providing more accurate and controllable environments for studying NDs. Finally, it discusses the application of these models in academic and industrial drug development, highlighting the potential of integrated microfluidic technologies in advancing research on neuropathogenesis and disease modeling.The review discusses the challenges in developing diagnostics and treatments for neurodegenerative diseases (NDs) due to their multifactorial pathogenesis. It highlights the emergence of advanced in vitro systems, such as microfluidic chips and organoid-on-a-chip models, which recapitulate patient-like pathophysiology and offer valuable insights for biomedical research and drug development. The review covers the interconnected pathogenic features of different NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). It details the specific pathogenic mechanisms in each disease, such as amyloid-β and tau protein dysfunction, neuroinflammation, mitochondrial dysfunction, and genetic alterations. The review also explores the limitations of current experimental models, particularly animal models, and emphasizes the advantages of microfluidic chips and organoids in providing more accurate and controllable environments for studying NDs. Finally, it discusses the application of these models in academic and industrial drug development, highlighting the potential of integrated microfluidic technologies in advancing research on neuropathogenesis and disease modeling.