Allergen specific Immunotherapy (ASIT) is the only systemic treatment for “type I hypersensitivity”, however, undesirable minor to severe allergic reactions are often witnessed during the course of therapy. Moreover, there are huge variations in the sensitivity of different patients to an allergen and the composition of allergenic extracts available for ASIT. For a better predictability of clinical outcome in ASIT and minimization of side effects, several combinatorial therapies have been devised which involve administration of allergen extracts with immunomodulatory or suppressive cytokines like TGF-β, IL-35 & IL-10. Recently, different endogenous specialized proresolving lipid mediators such as Lipoxins, Resolvins, Maresins and Protectins have shown promise as therapeutic agents in the resolution of allergic inflammation. Another growing concern is the problem of “Polyallergy”, which is basically a sensitivity of atopic individuals to two or more allergens. The precise diagnosis of polyallergy stands as a major challenge for clinicians, before they can initiate ASIT methodically. In this regard, Component Resolved Diagnosis (CRD) has emerged as a unique technological solution for detecting polyallergy, which can replace conventional serum specific IgE assays in near future. However, data interpretation in CRD is bit complex and ambiguous. In this review, we have provided the schematics of a prospective strategy, employing unique IgE epitope based allergen fragment arrays, which can enhance the resolution and predictability of CRD. We further suggest a technology for selecting a subset of novel hypoallergen molecules for delivering precise and thoroughly standardized ASIT with minimal side effects.