Global governance of pathogens such as Ebola virus and infectious diseases is central to global health, and to innovation in systems medicine. Worrisomely, the gaps in human immunity and healthcare services combined with novel pathogens emerging by travel, biotechnological advances, or the rupture of the host-species barrier challenge infectious diseases' global governance. Such biorisks and biothreats may scale up to global catastrophic biological risks (GCBRs) spatiotemporally, either as individual or as collective risks. The scale and intensity of such threats challenge current thinking on surveillance, and calls for a move toward pan-biosurveillance. New multilayered, cross-sectoral, and adaptable strategies of prevention and intervention on GCBRs should be developed, considering human hosts in entirety, and in close relationship with other hosts (plants and animals). This also calls for the "Humanome," which we introduce in this study as the totality of human subjects plus any directly dependent biological or nonbiological entities (products, constructs, and interventions). Surveillance networks should be implemented by integrating communications, diagnostics, and robotics/aeronautics technologies. Suppression of pathogens must be enforced both before and during an epidemic outbreak, the former allowing more drastic measures before the pathogens harbor the host. We propose in this expert review that microbiome-level intervention might particularly prove as an effective solution in medical and environmental scales against traditional, currently emerging, and future infectious threats. We conclude with a discussion on the ways in which the humanome and microbiome contest and cooperate, and how this knowledge might usefully inform in addressing the GCBRs, bioterrorism, and associated threats in the pursuit of pan-biosurveillance.