Japan’s healthcare digital transformation integrates top-down national initiatives, like the National Medical Information Platform, with diverse, locally driven regional networks. Although early efforts established over 200 regional collaboration networks, many proved unsustainable due to financial, infrastructure, and coordination challenges. This study uses a multi-method approach—including case studies, regulatory sandbox experiments, and international comparisons—to identify success factors for sustainable healthcare DX. Key findings highlight the need for adaptive governance, community engagement, and collaborative monetization. While top-down systematization works for smaller populations, it must be complemented by bottom-up mechanisms as stakeholder numbers grow.