ABSTRACT For more than 5 decades, the US has sought to lower cervical cancer deaths through screening; however, disparities remain. Introduction of oncogenic human papillomavirus (HPV)-based tests and HPV vaccines have expanded cervical cancer prevention strategies and changed screening and management guidelines. As technology, guidelines, and policies change, our MultilEvel OpTimization of the CeRvIcal Cancer Screening Process in Diverse Settings & Populations (METRICS) PROSPR II Research Center will elucidate multilevel factors that hamper or facilitate the cervical cancer screening process and reduce disparities in vulnerable populations. METRICS unites three PROSPR I Research Centers with demonstrated capability to provide validated data for a combined cohort of ~1.2 million screened and unscreened women. Our community settings represent 3 care delivery models?safety-net system, managed care system, and primary care provider networks in Texas, Washington, and Massachusetts. We will collect, harmonize, and document > 10 years of high-quality, comprehensive cervical cancer screening process data at the patient, provider, clinic, and system levels using a rich array of electronic clinical information systems and novel data sources. Our combined cohort is socioeconomically and geographically diverse and includes vulnerable groups such as HIV-infected and uninsured women. Our three interconnected observational projects are designed to understand how cervical cancer screening is delivered across our spectrum of delivery models, and how to optimize the screening process to reduce disparities. Innovative geospatial and Bayesian statistical methods in Project 1 will better elucidate at what levels variation in screening process occurs. Project 2 will investigate how multilevel programs and policies influence adherence to guidelines for average-risk women. Project 3 will inform precision screening for women with altered risk. Based on our observational findings, in years 4-5, we will design and implement pilot interventions leveraging IT-enabled tools to address key failures in the screening process and reduce disparities. Our transdisciplinary team has epidemiologists, primary and specialty care physicians, and intervention, implementation, and healthcare delivery experts. We are poised to efficiently evaluate the full cervical cancer screening process and provide expertise, leadership, and resources for cross-organ PROSPR II collaborations. Our cores and research projects will achieve our goals of advancing understanding of screening as practiced in community settings through: (1) analysis of multilevel observational data from our heterogeneous settings with diverse populations, (2) development and testing of impactful interventions to optimize the screening process, and (3) application of our novel observational projects and quality metrics to the cancer screening processes for other organs. Based on our successful experience leading and collaborating in PROSPR I, we thoughtfully organized our four cores to be able to launch research activities and contribute to trans-PROSPR II activities quickly and effectively.