We investigate known mechanisms for enhancing nuclear fusion rates at ambient temperatures and pressures in solid-state environments. In deuterium fusion, on which the paper is focused, an enhancement of >40 orders of magnitude would be needed to achieve observable fusion. We find that different mechanisms for fusion rate enhancement are known across the domains of atomic physics, nuclear physics, and quantum dynamics. Cascading multiple such mechanisms could lead to an overall enhancement of 40 orders of magnitude or more. We present a roadmap with examples of how hypothesis-driven research could be conducted in—and across—each domain to probe the plausibility of technologically-relevant fusion in the solid state.