The emergence of an advanced nuclear industry has renewed the pursuit of small modular and advanced reactor technologies to supply low carbon energy. By the same token, these developments potentially expose gaps in current safeguards practices, particularly for reactor designs utilizing novel coolants and fuel forms–underscoring calls for the early application of Safeguards-by-Design to effectively and efficiently detect diversion and misuse. Other innovations may necessitate additional measures to credibly assure the absence of undeclared activities. This paper discusses three types of advanced nuclear and nuclear-related technologies as illustrations of these challenges: 1) micronuclear reactors, 2) molten salt reactors, and on the balance-of-plant side, 3) thermal energy storage and dry cooling. It then identifies high-level safeguards development needs associated with these on-the-horizon technologies so as to elevate safeguards considerations in the minds of reactor developers and investors.