Chronic Inflammatory Response Syndrome (CIRS), commonly known as "Mold Illness," acquired from exposure to water-damaged buildings (WDB), represents a catastrophic failure of the innate immune system and cellular bioenergetics. The current integrative standard of care—Functional Medicine utilizing the Shoemaker Protocol—relies predominantly on biochemical interventions: systemic binders, targeted supplements, and dietary modulation to facilitate detoxification. While diagnostically precise and biochemically sound, this approach frequently encounters significant clinical ceilings in chronic, multisystemic cases. These limitations stem from a fundamental oversight: the inability of a metabolically exhausted host with compromised membrane transport and lymphatic stasis to execute complex biochemical detoxification pathways. This review argues for a paradigm shift toward a "Physics-First" hierarchy of care. By prioritizing advanced biophysical modalities—specifically Photobiomodulation (PBM), Hyperbaric Oxygen Therapy (HBOT) combined with Exercise with Oxygen Therapy (EWOT), Pulsed Electromagnetic Field (PEMF) therapy, and mechanical lymphatic/glymphatic clearance—clinicians can address the structural and energetic pathologies of CIRS that chemical agents cannot reach. We propose that restoring cellular voltage, reducing tissue hypoxia, and mechanically forcing detoxification pathways is the essential prerequisite for biochemical interventions to be effective.