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The emerging bioeconomy requires new supply chain paradigms for biomass materials to reach processing centers. Forest bio-hubs can be thought of as networks of collection points to facilitate biomass supply chains that feed from forest to central processing facilities. The design and functionality of forest bio-hubs depends on the form (e.g., vertically and horizontally integrated), and the quality and volume of feedstocks. In this paper we conceptually develop the potential role of forest bio-hubs. We then compare current bio-hub development in three U.S. regions—the Pacific Northwest, the southwest region, and the southeastern U.S. We use a “SWOT” framework to compare strengths, weaknesses, opportunities, and threats for each region. We consider transportation distances, topography, proximity to markets, harvesting methods, and wood products development. Innovation and adaptability would play key roles in forest bio-hub development, especially with dynamic conditions related to markets, wildfire risks, biomass utilization policy, and community socioeconomic factors.