α-Gal syndrome (AGS), a tick bite-associated allergy to mammalian meat, affects an estimated 450,000 Americans, with the highest prevalence concentrated in the US South and Southeast. The lone star tick (Amblyomma americanum), ubiquitous across the region, transmits AGS sensitization, making reexposure nearly inevitable for outdoor workers and residents. Current management relies on dietary avoidance of mammalian products of an indeterminant length, a recommendation that is neither practical in a region where mammalian meat is central to cuisine and culture nor evidence based regarding duration or necessity. In the absence of treatment options, patients are turning to alternative interventions such as acupuncture protocols that lack validation from controlled trials. Meanwhile, oral immunotherapy has demonstrated safety and efficacy for other immunoglobulin E-mediated food allergies, and individual case reports suggest desensitization may be feasible for AGS syndrome. The US South, with its high disease burden, clinical expertise, and patient populations, is uniquely positioned to lead the rigorous phase 1 and phase 2 trials needed to develop evidence-based treatment alternatives. Without such research, patients have only dietary restriction as an evidence-based option and may seek purported treatments that lack rigorous validation.