Abstract The tremendous global surging of the African Swine Fever Virus (ASFV) threatens pig industries worldwide. ASFV causes acute hemorrhagic fever in domestic pigs with near enough 100 % mortality, whereas immune in its natural host’s warthogs, bush-pigs, and the soft tick vector. ASFV is a large cytoplasmic double-stranded DNA virus that replicates mainly in macrophages. At present, infected animals can only be managed by quarantine and removal of infected animals as lack of effective vaccines and treatment. This review focus on mechanisms by which ASFV enter, replicate, modulate, molecular hijacking and overpowered the host immune system. Various machinery employed by ASFV discussed, such as overcoming barriers to replication in the monocyte/macrophage, inhibition of apoptosis, inhibition of inflammatory responses, ASFV adhesion protein CD2v. This review exposes ASFV evasion strategies and virus-host interactions, thus reveal promising vaccine development ideas.