The incidence and prevalence of food allergies is rising in children and adults, with peanut and tree nut beingthe most common food allergens. Current oral immunotherapy (OIT) protocols to desensitize patients to culpritallergens are associated with side effects that affect compliance and efficacy of OIT. More than 30% of patientswith food allergies are allergic to more than one food. Safer OIT protocols that minimize side effects whileimproving challenge thresholds to multiple allergens are needed to be able to address this food allergyepidemic. To address these challenges, we propose a multi-site phase 2 clinical study in children and adultswith peanut and tree nut allergies, using Omalizumab. Omalizumab is an anti-IgE monoclonal antibody whichdecreases free IgE in the blood and on mast cells and basophils, to minimize allergic inflammation. Wehypothesize that omalizumab pre-treatment followed by low dose maintenance therapy of multi-food OIT willminimize side effects while increasing the challenge thresholds for multi-food allergic patients. Our approach isto design a randomized, controlled Phase 2 study with two arms: Omalizumab plus low dose multi-food OITversus Omalizumab plus high dose multi-food OIT to contribute to the overall CoFAR objectives of improvingsafety and efficacy of OIT protocols. In implementing this study, we will create a comprehensive dataset ofclinical outcomes from multiple sites within CoFAR and patient samples to understand mechanisms of treatmentsuccess. Our specific aims are 1) Test whether treatment of children and adults with Omalizumab and food OITto peanut and walnut increases the ability to pass a food challenge to 2g of at least 2 allergens: peanut andwalnut; 2) Determine whether treatment of children and adults in low vs high maintenance arms of multi foodOIT with omalizumab is safer; and 3) Evaluate to what degree laboratory and clinical testing methods (i.e.endotypes and phenotypes of food allergic patients) are associated with safety and efficacy outcomes (inSpecific Aims 1 and 2) in low dose versus high dose maintenance groups. If the aims of our proposal are met,we will determine the optimal maintenance dose protocol for desensitization to multiple foods with omalizumabthat causes minimal side effects with optimal success rates.