Mushrooms have emerged as potent bioactive resources in the evolving landscape of personalized nutrition and functional food development. This chapter explores the integration of mushrooms into tailored dietary strategies aimed at enhancing individual health outcomes and preventing chronic diseases. With a rich profile of bioactive compounds—such as polysaccharides (e.g., β-glucans), polyphenols, ergothioneine, and various vitamins and minerals—mushrooms exhibit immunomodulatory, antioxidant, anti-inflammatory, and antidiabetic properties. Advances in nutrigenomics and metabolomics have further emphasized the potential of mushrooms to meet specific nutritional needs based on genetic and metabolic profiles. This chapter discusses key mushroom species used in functional foods, their health-promoting constituents, mechanisms of action, and current applications in customized dietary formulations. Additionally, it examines the technological innovations enabling mushroom incorporation into food matrices, including encapsulation and fermentation. Challenges and future perspectives related to standardization, bioavailability, regulatory aspects, and consumer acceptance are also addressed. Overall, this chapter highlights the promising role of mushrooms as functional ingredients in the personalized nutrition paradigm, contributing to precision health and sustainable food systems.