The complexity of global health challenges requires integrated approaches that crosses traditional boundaries. One Health (OH) offers a holistic approach to address health issues at the crossroads of human, animal, and environmental domains. Antimicrobial Resistance (AMR), a prime example of a cross-sectoral issue and OH challenge, highlights the need for coordinated interventions that consider multiple stakeholders. Current approaches to improve OH challenges and AMR have limited success, often due to a lack of a structured theoretical approach that informs the design and development of solutions for long-term sustainability. Existing frameworks focus primarily on human or veterinary sectors in isolation, leaving a gap in comprehensive, integrated approaches that align with OH principles. The proposed framework addresses this gap by offering a structured approach to both implementing and evaluating interventions that consider all three sectors. This paper proposes the HEARTf of OHC (), a user-centered design approach aimed at developing sustainable and innovative OHC interventions. The HEARTf of OHC integrates knowledge from social sciences, computer science, industrial design, pedagogy, and health sciences to create context specific solutions that address the specific needs of end-users in the human, animal, and environmental sectors. Additionally, this paper reviews existing frameworks addressing AMR, identifies limitations and outlines the need for a transdisciplinary approach when tackling OHC. By emphasizing the importance of the user-centered design, transdisciplinarity, and continuous evaluation, the HEARTf of OHC aims to bridge the gap between current strategies and improve the development and evaluation of innovative solutions or services. The HEARTf of OHC is a generalizable framework for the design, implementation, and evaluation of OH interventions, where we use AMR as a case study to demonstrate its application.