Many health systems are working to become learning health systems (LHSs), which aim to improve the value of health care by rapidly, continuously generating evidence to apply to practice. However, challenges remain to advance toward the aspirational goal of becoming a fully mature LHS. While some important challenges have been well described (i.e., building system-level supporting infrastructure and the accessibility of inclusive, integrated, and actionable data), other key challenges are underrecognized, including balancing evaluation rapidity with rigor, applying principles of health equity and classic ethics, focusing on external validity and reproducibility (generalizability), and designing for sustainability. Many LHSs focus on continuous learning cycles, but with limited consideration of issues related to the rapidity of these learning cycles, as well as the sustainability or generalizability of solutions. Some types of data have been consistently underrepresented, including patient-reported outcomes and preferences, social determinants, and behavioral and environmental data, the absence of which can exacerbate health disparities. A promising approach to addressing many challenges that LHSs face may be found in dissemination and implementation (D&I) science. With an emphasis on multilevel dynamic contextual factors, representation of implementation partner engagement, pragmatic research, sustainability, and generalizability, D&I science methods can assist in overcoming many of the challenges facing LHSs. In this article, the authors describe the current state of LHSs and challenges to becoming a mature LHS, propose solutions to current challenges, focusing on the contributions of D&I science with other methods, and propose key components and characteristics of a mature LHS model that others can use to plan and develop their LHSs.