This chapter provides a comprehensive analysis of risk factors and their interconnected relationships in Long COVID fatigue. Through examination of current research and clinical evidence, the text explores four major categories of risk factors: demographic, clinical, biological, and psychological-social. The chapter presents a detailed analysis of how female sex, age, disease severity, immune dysregulation, and mental health status contribute to the development and persistence of Long COVID fatigue. Central to the discussion is a sophisticated network visualization that maps the complex interactions between these various risk factors, illustrated through Fig. 12.1. The analysis demonstrates how factors such as clinical severity and immune response create bidirectional relationships with other variables, forming an intricate web of associations. The chapter emphasizes the importance of understanding these interconnections for developing effective treatment strategies, supported by recent research findings from multiple studies. This comprehensive examination of risk factors and their relationships provides crucial insights for healthcare providers and researchers working to understand and treat Long COVID fatigue, highlighting the necessity of considering multiple factors simultaneously in clinical assessment and treatment planning.