Omalizumab is a newly FDA approved anti-IgE therapy for allergen agnostic treatment of single or multiple food allergies in patients ages >1 year. Evaluate the cost-effectiveness of omalizumab as a food allergy treatment. Health and economic outcomes were evaluated in Markov cohorts of simulated food allergic infants randomized to receive omalizumab using a 15-year time horizon. Monte Carlo simulation was used (n=40,000 subjects) to evaluate cost-effectiveness from a societal perspective, incorporating both a family-level and individual-level analysis. Family-level analysis was included to incorporate broad perspective for health utility change, given treatment effects likely benefit all parties at home (e.g., caregivers, siblings, spouses), not just the patient, representing the sum of changes in all such persons. Supplemental analyses explored lower omalizumab cost and home initiation. Deterministic and probabilistic sensitivity analyses were performed. In the family-level cohort analysis, omalizumab exceeded cost-effectiveness thresholds ($185,183/QALY). Comparing the omalizumab strategy (OMA) to the non-omalizumab strategy (NOMA), the cost of OMA exceeded NOMA ($315,020 vs $136,609) with greater incremental effectiveness (12.668 QALY vs 11.699 QALY). In the individual-level analysis, the cost-effectiveness of OMA was $573,698/QALY. In base-case assessments, OMA was cost-effective (WTP, $100,000/QALY) at a health state utility improvement of 0.265. OMA's value-based cost ranged from $14,166-$23,791 when considered at the individual and family-unit levels. Requiring OMA administration in-clinic was not cost-effective (ICER, $260,239). In the base-case and at current pricing, omalizumab is not cost-effective, but could be at a lower retail price or if use creates large health utility shifts in the family and patient.