Background: Without consideration for the food system in which healthy food-store interventions (HFIs) are implemented, their effects are likely to be unsustainable. Co-creation of HFIs by interventionists and food-store actors may improve contextual fit and therefore the effectiveness and sustainability of interventions, but there are few case studies on the topic. This study aims to provide insights into the integration of knowledge from contextual actors into HFI designs, through a co-creative process, to illustrate potential challenges, advantages, and outcomes. Methods: We describe the co-creative design of an HFI in a Dutch supermarket chain, conducted through three increasingly in-depth design phases. Each phase consisted of a cycle of theorizing (gather insights from literature, feedback, and pilot studies), building (develop intervention designs), and evaluating (interviews or workshops with supermarket actors, to explore barriers and facilitators for sustainable implementation), feeding back into the next phase (drafting adapted intervention designs, based on feedback, and research input). Interview transcripts underwent a qualitative content analysis. Results: We co-creatively designed four types of interventions to promote healthier food choices in supermarkets: (1) price strategies, (2) product presentation and positioning, (3) signage, and (4) interactive messaging. Interventions were aligned with the culture, structures and practices of the supermarket chain, while simultaneously challenging these system characteristics. For example, the idea of price promotions on healthy foods was well-received and encountered only practical barriers, which were easily resolved. However, the specification of tax-like price increases on unhealthy foods led to substantial resistance on cultural and commercial grounds, which were resolved through support from a key supermarket actor. Conclusion: Our results illustrate the potential benefits of co-creation approaches in HFI design. We reflect on the value of more easily accepted interventions to develop collaborative momentum and more radical interventions to drive more substantial changes.