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Lassa fever is a viral hemorrhagic, Rodent-borne disease caused by the Lassa virus. It is mainly endemic in the Sub-regions of West Africa, including Nigeria due to the predominance of the zoonotic host in the region. Treatment options in Nigeria presently are limited and mortality rate is also high, due to lack of an approved preventive Vaccine, with Ribavirin being the major therapy for now. Our analytical findings unveiled that the genetic diversity among the different strains of Lassa fever has the ability to circumvent the immune system and this poses a critical challenge to the development of therapeutics for the disease. Hence understanding the biochemical mechanism of host immune invasion by the virus and its genetic polymorphism is key in the development of more effective therapeutics to combat this deadly virus, especially now that recent reviews have identified the Lassa fever Nucleoprotein (which functions in several aspects of the viral life cycle) as a novel target for therapeutics. Moving forward, Lassa fever Nucleoproteins inhibitors inhibitors can be employed as effective therapeutics to potentially inhibit the disease replication. Effective preventive measures, vaccine development, Repurposing of existing drugs using activity or in silico-based and computational bioinformatics, would be critical in the development of novel therapeutics for Lassa fever treatment.