Manufacturing is a cornerstone of economic stability and growth, employing over 12.7 million workers in the United States alone and contributing significantly to the country’s GDP. However, it also represents one of the largest consumers of energy, using approximately 30% of the nation’s total energy supply, and is a major source of environmental burdens, including greenhouse gas emissions, waste, and resource depletion. This dual role of manufacturing—as both a key economic driver and a significant environmental impactor—underscores the need for innovative approaches that can enhance sustainability while also consideringresilience. Sustainable manufacturing aims to reduce environmental degradation and optimize resource use, while resilient manufacturing systems must maintain operational continuity and protect jobs during unexpected disturbances, such as supply chain disruptions, machine disruptions or natural disasters. Yet, achieving both sustainability and resilience within manufacturing systems presents a complex and often quantitatively ambiguous challenge, with few frameworks that can simultaneously address these objectives. This research investigates a bio-inspired approach to manufacturing design, drawing from the principles of ecological resilience and sustainability found in nature. By studying forty-four manufacturing floor plans, we evaluate the potential of bio-inspired design principles to improve both sustainability and resilience and compare them to traditional manufacturing metrics. The bio-inspired methodology leverages Ecological Network Analysis (ENA), a tool used to study ecological networks such as food webs, which are known for their resilience to disturbances and ability to sustain diverse functions. ENA offers valuable insights into how natural systems achieve balance and stability, and these insights can be translated into manufacturing system designs. Specifically, we examine traditional manufacturing metrics, such as convertibility, throughput, and capacity utilization, and correlate these with ecological characteristics to bridge the gap between manufacturing goals and ecological design principles. Through scenario testing under various simulated disturbances, we assess whether bio-inspired manufacturing system designs outperform conventional approaches in maintaining productivity and adaptability. Results indicate that bio-inspired designs often foster interdependencies that enhance resilience and support cyclical pathways—key components of the circular economy. For example, systems designed with bio-inspired principles are shown to possess higher convertibility, allowing them to reconfigure quickly in response to changing demands or disruptions. This adaptability also supports sustainable practices by reducing waste and extending the lifecycle of resources within the system. The findings of this study contribute to the early-stage assessment of manufacturing systems by introducing low-data metrics that capture both resilience and sustainability, facilitating the design of systems that can achieve a well-rounded operational balance. This bio-inspired framework provides manufacturers with a quantitative, systematic approach to embedding sustainable and resilient principles into their operations, offering a pathway toward more robust, environmentally responsible manufacturing practices that are adaptable to future challenges.