Our study aims to investigate the potential of inflammatome—characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, and IgA), and highlighting autoantibody type receptor-based biomarkers (anti-M3, anti-M4, and anti-β2AdR)—for evaluating condition progression in patients with ME/CFS and identifying the optimal selection to assess prospective clinical tests for ME/CFS. Here, IL21 is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.