Background Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. Objective The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. Methods This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. Results An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. Conclusions The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory–based mHealth strategy.