Patient healthcare personalization provides new opportunities for health care systems in their pursuit of better patient outcomes and commitment to quality and safety. Much like the recent expansion of product customization, healthcare personalization has been expanding lately due to a variety of factors including technological advances that connect data, people, and systems. Much of the existing research has viewed service variability as something negative that must be controlled. However, customer variability in service needs provides an opportunity to deliver more value for patients through personalization of services. This chapter will examine patient healthcare personalization and the design of systems for service customization within smart cities. The chapter discusses patient healthcare personalization and service design, focusing on the concept of patient variability and the use of innovative computer and information science and engineering approaches to support the transformation of health and medicine.