The clinical picture of multimorbidity is heterogeneous and it is characterized by great complexity. Precision medicine is an innovative approach to provide personalized care focused on individual characteristics and to deliver the right treatments, at the right time, to the right person. The precision medicine approach, which represents an epochal change in the field of chronic diseases, has been poorly implemented in patients with multimorbidity. Several factors can limit this application. First, the precision medicine approach has been successfully applied in the treatment of mono-factorial diseases while multimorbidity is multifactorial. Second, there is lack of understanding of risk factors in the development and evolution of multimorbidity. Third, precision medicine is mainly focused on understanding genetic aspects of diseases and neglects other characteristics contributing to the definition of individual profiles. Finally, individual pathways may lead to the development of different multimorbidity phenotypes. A possible solution to simplify the application of precision medicine to this condition is to reduce its complexity and to find homogeneous patterns of chronic diseases that may work as targets of preventive and therapeutic strategies. This approach can lead to better understanding how these factors interact at individual level and to define interventions that might target multimorbidity.