Parasites developed several strategies for their survival and host tissue invasion. Helminths express potent molecules mainly for immunomodulation, which is why they stay in their hosts for years. Helminths display several mechanisms not only to evade host immune response(s), but also to preserve the host for as long as they could live. In contrast, protozoa evolve several policies primarily for pathogenesis, and invasion. Therefore, variable clinical manifestations are reported in protozoal diseases. Both symptomatic and asymptomatic cases are commonly observed in amoebiasis, giardiasis, trichomoniasis, cryptosporidiosis and toxoplasmosis, while mild, moderate, and severe cases occur in malaria, leishmaniasis, African sleeping sickness and Chagas' disease. This was primarily attributed to strains variability and to a lesser extent, to host immune response(s). With recent evolutionary technology in molecular parasitology and bioinformatics, several molecules are established as virulence factors. These factors encourage researchers and scientists to develop novel drug targets and/or vaccine candidates. The present review aims to highlight, and review virulence strategies adapted by parasites to invade host tissue, enhance its replication and spread, as well as other processes for immunomodulation or immunoevasion of host immune response(s).