The intersection of Long COVID and tick-borne diseases (TBDs) presents a complex, multi-systemic challenge that demands a nuanced understanding of their shared mechanisms, diagnostic intricacies, and individualized treatment approaches. Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, mirrors chronic TBDs in its diverse clinical presentations, including chronic fatigue, brain fog, and neurologic and gastrointestinal dysfunction. Both conditions are driven by mechanisms such as spike protein interactions with ACE2 receptors, viral or bacterial reservoirs, microclots from endothelial inflammation, and the reactivation of dormant infections like Epstein-Barr virus, cytomegalovirus, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Additional contributors include microbiome dysregulation, epithelial barrier disruption, immune dysregulation (T- and B-cell exhaustion, autoimmunity, and Mast Cell Activation Syndrome), prolonged cytokine-driven inflammation, and epigenetic modulation. The vagus nerve, a critical regulator of the autonomic nervous system and inflammation, is notably impacted by both SARS-CoV-2 and Lyme disease, leading to symptoms like tachycardia, postural orthostatic tachycardia syndrome (POTS), and cognitive impairment when damaged. Diagnosing Long COVID requires distinguishing between Type 1, driven solely by COVID-related factors (microclots, reservoirs, spike protein), and Type 2, complicated by concurrent TBDs, other infections, environmental toxicities, or structural issues. Type 1 often responds to protocol-driven treatments, while Type 2 typically requires tailored interventions due to its complexity. The heterogeneity of these conditions underscores the limitations of standardized protocols, as multi-systemic inflammation and concurrent infections vary widely among individuals. This presentation explores the overlapping pathophysiology, the pivotal role of the vagus nerve in modulating systemic inflammation, and the necessity of personalized treatment strategies to address the unique root causes and downstream effects in each patient.