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Background: Asthma is a highly prevalent disease, one of the chronic diseases with the highest economic costs; thus, it imposes a high economic burden on society, the healthcare system, patients, and third-party payers. Contrary to this study, until now, systematic reviews of economic evaluations (EEs) of treatments for severe asthma have not been exclusively focused on biological treatments, and have included a small number of studies and only model-based EEs., Methods: This study systematically reviews EEs of biological therapies for severe asthma published until December 2022 using PRISMA guidelines. The review analyzes the cost-effectiveness of biologicals in comparison to SOC, or SOC plus OCS. The quality of the EEs is assessed using Consensus on Health Economics Checklist extended (CHEC-extended)., Results: Thirty-nine studies were eligible: 15 based on a Markov model, and 19 trial-based; eight adopting societal and NHS perspectives, and seven the payer's perspective. The reviewed EEs addressed cost-effectiveness, cost-utility, and incremental costs and outcomes comparison. Their findings were mainly expressed through ICER-incremental cost-effectiveness ratio (24 studies: 13 concluded that biological were cost-effective) and cost comparison analysis (14 studies: 6 concluded that biological were cost-effective), and were sensitive to a wide variety of factors (e.g. medication cost, treatment response, time horizon, utility benefits, mortality, exacerbation rate, discount rate, etc.)., Conclusions: There has been some ambiguity concerning the EE of biological therapies due to variation in choice of study design and contradictory results. Nevertheless, it can be concluded that biological treatments improve health outcomes, in many contexts at a high cost.