What makes Silicon Valley the hottest high-tech cluster in the world and can such a highly successful high-tech cluster develop elsewhere? If so, what are the prerequisites to establish a comparable nexus of innovation and which elements are the most significant in order to attract the best and brightest minds? Expanding on previous research we outline 15 hypotheses that embody key success factors in the context of the Bay Area and help us to derive implications on what a potential Silicon Valley candidate must consider. Following a conceptual mapping approach supplemented by qualitative interviews with actors in Silicon Valley, we posit our hypotheses for further empirical testing and cross-cluster comparison. We argue for a combination between bottom-up cultivation and top-down support that enables a system of serendipity and attracts and maintains world-class talent. Our chapter contributes to ongoing research on replicating Silicon Valley, building high-tech clusters and entrepreneurial ecosystems.