This paper presents a biodesign pedagogical framework that integrates experiential learning, metagenomic sequencing, and speculative design through the study of London’s rainwater microbiome. While urban systems typically treat rainwater as an inert resource, this research frames it as a dynamic “living medium” hosting diverse microbial life. Utilizing environmental DNA (eDNA) analysis, postgraduate Biodesign students characterized bacterial, fungal, and microalgal taxa, identifying specific potentials for nutrition, biostimulation, and bioremediation. These microbial insights were subsequently applied to the development of regenerative food systems and urban ecological interventions. By positioning rainwater as an active ecological collaborator, the curriculum enabled students to navigate more-than-human agency, ecological uncertainty, and systems thinking through direct experimentation. This study demonstrates how the integration of genomic tools into design education expands ecological literacy and supports multispecies practices. We conclude by analysing the pedagogical process phases and student outcomes, highlighting how rainwater serves as a critical interface between climate futures, urban metabolism, and living design.