In the midst of modernization of human lifestyle with the profound effect of sophisticated technologies, pathogens in parallel have also evolved gradually to stay masked and smuggled their ways into our lives. Of different pathogens, zoonotic microbes are the most challenging to control, attributed to faulty surveillance systems to monitor the emergence of any pathogens at the human-animal interface. Amongst different infectious diseases in bovines, mastitis is a prototypic emerging and reemerging disease caused by pathogenic microbes that have overcome a series of hierarchical barriers resulting in zoonotic transmission. Although it has been annoyingly persistent since ancient times, it has never been a focus for desperate measures. However, the most critical is the chronic asymptomatic subclinical mastitis that results in cut-by-cut torture to not only the animals but also to the global economy. Despite the rapid technological advancement, identification of mastitis in subclinical form at the local community level is still improbable, leading to a high chance of the pathogenic and antimicrobial spillover. Understanding the complex sociological and ecological factors influencing disease transmission risks and pathogen containment remains unelucidated. Multiple factors are essential for the successful detection and containment of pathogens that have prompted the initiation of the “One Health” approach. Nevertheless, there is a lack of collaborative approach between the local and global strategists to suggest and implement checkpoints at different horizons to control mastitis. Here, we review the evolution of these pathogens in the reservoir host, their zoonotic potential and the pros and cons of current management strategies. We also address the extent of success in implementing a concerted approach like “One Health One Welfare,” which calls for interdisciplinary collaboration between professionals in human, animal and environmental health along with multi-omics to keep the pathogens at bay.