This systematic review comprises the literature that evaluates the cost-effectiveness of ATMPs in rare disease treatment, specifically detecting the three most frequent macro-diagnoses: rare blood cancers (B-cell acute lymphoblastic leukemia-ALL, diffuse large B-cell lymphoma-DLBCL, multiple myeloma-MM, mantle cell lymphoma-MCL, follicular lymphoma-FL, and hemophilia B); spinal muscular atrophy type I- SMA; and retinal diseases with RP E65-mutation treatment. Here, SMN1 is linked to B-cell acute lymphoblastic leukemia.