Understanding microbe-host interactions has been limited by technological barriers in simultaneously observing both partners within complex biological systems. Traditional methods often analyze microbial and host components separately, missing critical spatial and temporal dynamics of their interaction. We are developing innovative co-detection technologies that can jointly capture and quantify the molecular activities of microbes and hosts together in situ. This will enable us to systematically map interaction mechanisms in various biological contexts, from gut microbiota influencing host metabolism to pathogens evading immune detection. The development of these co-detection technologies will not only reveal fundamental insights into microbe-host communication and accelerate the discovery of diagnostic biomarkers and therapeutic targets.