As global seafood demand intensifies with population growth and nutritional needs, developing sustainable production methods is essential for securing future food systems. In the U.S., seafood consumption is projected to double by 2050, making cell-based seafood a promising, sustainable alternative. While advancements in scalable cell-based seafood technologies are progressing, significant challenges remain, particularly in regulatory, socio-political, and consumer acceptance areas. The success of cell-based seafood as a sustainable food source heavily depends on consumer acceptance, yet public attitudes toward this innovation are not well understood. To address this gap, a survey was conducted via Qualtrics with a nationally representative sample of 2,121 U.S. respondents. This study provides critical insights into consumer attitudes toward cell-based seafood by examining socio-demographic influences and adoption barriers. Results indicate a complex landscape where willingness to try these cell-based seafood varies significantly across demographics, with younger consumers, urban residents, and environmentally-conscious consumers displaying a higher acceptance for cell-based seafood. Additionally, consumers are already inclined to try innovative foods and current seafood eaters are more open to cell-based options. However, cell-based seafood adoption barriers are artificialness, unfamiliarity, and lack of exposure. Findings from this study emphasize that fostering consumer trust in cell-based seafood requires concerted efforts in regulatory clarity, and educational initiatives that enhance familiarity. On the other hand, Total Unduplicated Reach and Frequency (TURF) analysis shows that food safety is the primary factor driving consumer acceptance, highlighting the need for transparent, safety-focused communication. These insights inform actionable strategies for industry stakeholders and policymakers, advancing a market integration framework essential to positioning cell-based seafood as a viable and sustainable component of the U.S. food system.