The field of individualized, or N-of-1, therapy development is growing and increasingly gaining attention as a novel option for people with serious diseases, caused by unique genetic variants for whom approved therapies are not available. The N-of-1 taskforce of the International Rare Disease Research Consortium previously outlined a roadmap of aspects involved in N-of-1 therapy development and implementation. Here, this follow-up paper looks forward and reflects on how to address existing gaps to advance the current state of individualized interventions toward an integrated and sustainable treatment development model. It discusses what needs to be established for N-of-1 therapies to be developed and utilized at a larger scale, which involves features like sustainability; safety; efficacy; regulatory aspects; dedicated registries and data sharing; tools; long-term treatment monitoring; partnering with patient advocates; and reimbursement models. It closes with recommendations to shape the future of individualized therapies, focusing on ethical implications, education, creation of tools, incentives for data sharing, and innovative payment models.