The prevalence of knee osteoarthritis (KOA) in the adult population is high and patients profit from individualized therapy approaches. Just-in-time adaptive interventions (JITAIs) are upcoming digital interventions for behavior change. This systematic review summarizes the features and effectiveness of existing JITAIs regarding important physiological health outcomes and derives the most promising features for the use case of KOA. The electronic databases PubMed, Web of Science, Scopus, and EBSCO were searched using keywords related to JITAIs, physical activity (PA), sedentary behavior (SB), physical function, quality of life, pain, and stiffness. JITAIs for adults that focused on the effectiveness of at least 1 of the selected outcomes were included and synthesized qualitatively. Study quality was assessed with the Quality Assessment Tool Effective Public Health Practice Project. A total of 45 studies with mainly weak overall quality were included in this review. The studies were mostly focused on PA and SB and no study examined stiffness. The design of JITAIs varied, with a frequency of decision points from a minute to a day, device-based measured and self-reported tailoring variables, intervention options including audible or vibration prompts and tailored feedback, and decision rules from simple if-then conditions based on 1 variable to more complex algorithms including contextual variables. The use of frequent decision points, device-based measured tailoring variables accompanied by user input, intervention options tailored to user preferences, and simple decision rules showed the most promising results in previous studies. This can be transferred to a JITAI for the use case of KOA by using target variables that include breaks in SB and an optimum of PA considering individual knee load for the health benefits of patients.