The healthcare sector evolves constantly, driven by technological advancement and innovative solutions. From remote patient monitoring to the Internet of Things (IoT), Artificial Intelligence (AI), personalized medicine, mobile health, and electronic records systems, technology has improved patient outcomes and enhanced care delivery. These technologies have shifted the healthcare ecosystem to be more patient-centered, focusing on meeting the patient's needs rather than the needs of the individual organizations within it. However, this transformative shift experienced by the healthcare industry is associated with multiple challenges due to the inherent complexity and fragmentation of the healthcare ecosystem. This dissertation addresses three healthcare ecosystem challenges that significantly impact patients. The first challenge addressed is the problem of counterfeit or falsified drugs that represent a threat to public health, resulting from the vulnerabilities in the pharmaceutical supply chain, notably centralized data management and the lack of transparency. The second challenge addressed is the problem of healthcare data fragmentation that thwarts care coordination and impacts clinical efficiency. This problem results from the dynamic and complex patients' journey in the healthcare system, shaped by their unique health needs and preferences. Patient data are scattered across multiple healthcare organizations within centralized databases and are ruled by policies that hinder data sharing and patients' empowerment over their data. The third challenge addressed is the confidentiality and privacy of healthcare data that, if compromised, shatter the trust relationship between patients and healthcare stakeholders. This challenge results from the healthcare organizations' poor data governance that increases the risk of data breaches and unauthorized access to patient information.The blockchain has emerged as a promising solution to address these critical challenges. It was introduced into the healthcare ecosystem with the promise of enforcing transparency, authentication, security, and trustworthiness. Through comprehensive analysis and case studies, this dissertation assesses the opportunities and addresses the challenges of adopting the blockchain in the healthcare industry. We start with a thorough review of the state of the art covering the blockchain's role in improving supply chain management and enhancing the healthcare delivery chain. Second, we combine theoretical and real-world application studies to develop a guideline that outlines the requirements for building a blockchain-based supply chain. Third, we propose a patient-centric framework that combines blockchain technology with Semantic technologies to help patients manage their health data. Our fourth contribution presents a novel approach to data governance by developing a blockchain-based framework that improves data security and empowers patients to participate actively in their healthcare decisions. In this final contribution, we widen the scope of the proposed framework to include a roadmap for its adoption across diverse domains (banking, education, transportation, and logistics, etc.).