The shrimp sector has been one of the fastest growing agri-food systems in the last decades, but its growth has entailed negative social and environmental impacts. Sustainable intensification will require innovation in multiple elements of the shrimp production system and its value chain. We use the case of the shrimp sector in the Mekong Delta in Vietnam to explore the constraints in the transition to sustainable intensification in shrimp farming, using an analytical framework based on innovation systems thinking, i.e., an aquaculture innovation systems framework. Using this framework, we conduct a systemic diagnostic of blocking mechanisms, interrelated sets of constraints within the aquaculture sector that hinder a transition toward sustainable intensification. Our findings show that the major constraints are institutional, with limited enforcement of the regulatory framework for input quality control, disease control, and wastewater management, and a lack of coordination between government bodies to design and enforce this framework. At farm level, limited access to capital favors pond mismanagement and the use of low-quality inputs. The absence of multi-stakeholder initiatives to foster dialog between actors in the value chain constrains the response to new regulations dictated by international market demand. Because of shrimp farming’s connectivity with the wider ecosystem, sustainable intensification in shrimp farming will require collective management of water resources at the landscape level for disease and water pollution control. Ecological principles for pond management need to be promoted to farmers in order to reduce farmers’ inefficient practices and build their capacity to understand new techniques and inputs available in the Vietnamese market. Our paper demonstrates for the utility of a multi-level, multi-dimension, and multi-stakeholder aquaculture innovation systems approach to analyze and address these blocking mechanisms in the transition to sustainable intensification in shrimp farming and aquaculture more broadly.