This open access handbook redefines science diplomacy in an era of geopolitical rivalry, rapid technological change, and fragmented global governance. Moving beyond state-centric models, it advances a polycentric framework where authority and expertise are distributed across diverse actors. Combining conceptual insights with empirical case studies, it examines securitization, emerging diplomatic players, and technology as a site of power—offering a rigorous guide for navigating cooperation under conditions of uncertainty, asymmetry, and disruption.