<p>We are living in an era where food allergy is increasingly prevalent, and shrimp allergy (SA) is among the most common and potentially severe reactions worldwide. Significant efforts have been made to improve diagnostic accuracy and treatment options. However, diagnosing SA remains challenging due to its diverse clinical presentations and the complexity of shrimp allergens. The pathogenesis of SA is complicated by various allergens sensitization, epithelial barrier disruption and gut microbiota dysbiosis. To date, at least ten shrimp allergens have been identified, but sensitization profiles vary significantly across populations. Promising novel immunotherapy approaches have been explored, showing potential in murine models. The use of physiologically relevant experimental systems, from in vivo models (e.g., murine studies) to advanced ex vivo human-based techniques (including organoids, organ-on-a-chip platforms, and tissue slice cultures), offers promising alternative for studying biological processes that are difficult to investigate directly in humans. These models have emerged as a valuable tool in food allergy research by providing critical insights into food-gut interactions, gut microbiota-host dynamics epithelial barrier integrity and cross-talk between epithelia and immune cells, and signaling and inflammatory markers. This review aims to summarize recent advancements in the diagnosis and treatment of SA, and the potential in vivo/ex-vivo models in SA research.</p>