Although shrimp processing wastes have been studied as source of high-value products at lab-scale, no contributions are found in the literature regarding the energetic and safety performance of shrimp-based biorefineries at pilot or large-scale. This works is focused on the inherent safety assessment and exergy analysis of a pilot-scale biorefinery designed to produce shrimp meat and four by-products: chitin, chitosan, nitrogenous extract, and astaxanthin. Total irreversibilities, exergy losses, exergy of wastes and utilities were calculated for stages and the overall process using mass and energy balances of the biorefinery. The hazards associated with chemicals and process conditions were analyzed through substance properties and process data. A Numerical Descriptive Inherent Safety Technique (NuDIST) score of 557.23 suggested a moderate level of risk for the biorefinery compared to other processes, reaching chemical and process safety scores of 185.88 and 371.35, respectively. Sections (b) and (c) were identified as major hotspots from a safety point of view. The overall exergy efficiency was quantified at 25.61%, which is higher than the chitosan-from-exoskeleton linear production chain (4.58%). The highest exergy losses were found on stages as deacetylation, fresh shrimp washing and deproteinization stages. The beheading stage most contributed to irreversibilities, with 98.315%, followed by sorting, with 1.653%. These results could identify opportunities for improvement from an exergy and safety point of view by mapping less efficient and hazardous stages.