Guidelines for optimal cancer screening in older adults remain unclear, particularly for adults over the age of 75. While cancer screening in older adults may benefit some in good health, it may cause unnecessary burdens in others with limited life expectancy. Thus, a systematic approach to enable individualized cancer screening decisions in older adults is needed. We suggest a framework that guides such decisions through evidence-based approaches from multiple interactions, and that involves the patient, clinician, and healthcare system. An individualized approach considers differences in disease risk rather than the chronological age of the patient. This paper presents a comprehensive framework that depicts the independent and converging levels of influences on individualized cancer screening decisions in older adults. This Individualized Decisions for Screening (IDS) framework recognizes the reality of these interrelationships, including the tensions that arise when behaviors and outcomes are valued differently at the patient, clinician, and healthcare organization levels. Person-centered approaches are essential to advancing multilevel research of individualized cancer screening decisions among older adults.