Teachers, schools, districts, states, and technology developers endeavor to personalize learning experiences for students, but definitions of personalized learning (PL) vary and designs often span multiple components. Variability in definition and implementation complicate the study of PL and the ways that designs can leverage student characteristics to reliably achieve targeted learning outcomes. We document the diversity of definitions of PL that guide implementation in educational settings and review relevant educational theories that could inform design and implementation. We then report on a systematic review of empirical studies of personalized learning using PRISMA guidelines. We identified 376 unique studies that investigated one or more PL design features and appraised this corpus to determine (1) who studies personalized learning; (2) with whom, and in what contexts; and (3) with focus on what learner characteristics, instructional design approaches, and learning outcomes. Results suggest that PL research is led by researchers in education, computer science, engineering, and other disciplines, and that the focus of their PL designs differs by the learner characteristics and targeted outcomes they prioritize. We further observed that research tends to proceed without a priori theoretical conceptualization, but also that designs often implicitly align to assumptions posed by extant theories of learning. We propose that a theoretically guided approach to the design and study of PL can organize efforts to evaluate the practice, and forming an explicit theory of change can improve the likelihood that efforts to personalize learning achieve their aims. We propose a theory-guided method for the design of PL and recommend research methods that can parse the effects obtained by individual design features within the "many-to-many-to-many" designs that characterize PL in practice.