Brucellosis is a zoonotic infection transmitted to humans from infected animals and is one of the widely spread zoonoses. Recently, six species were recognized within the genus Brucella wherein B. melitensis, B. suis and B. abortus are considered virulent for humans. While these species differ phenotypically by their pattern of metabolic activities, there has been an imperative need to understand pathogenesis of Brucella species. It has been foreseen that creating a human vaccine for Brucellosis would entail decreased dose of antibiotics. However the emerging role of Brucella pathogenesis still centers on isolation of the organism and various diagnostic tests thereby leading to varying strategies of treatment cycle. In view of disease heterogeneity, we focus systems and synthetic biology challenges that might improve our understanding the Brucella pathogenesis.