Background: Mortality from colorectal cancer (CRC) in the Northwest Territories (NWT), a northern region of Canada, is nearly double the national rate. While mortality could be reduced with greater adherence to CRC screening, this requires colonoscopy access which is limited, and difficult to predict in a complex remote health system. Simulation modeling has been used to plan CRC screening but the impact on decision-making and utility in complex remote health system is unclear. Aim: This thesis aims to estimate the colonoscopy requirements and outcomes of CRC screening in the NWT using simulation modeling in a way that will inform feasible patient-centered strategies to enhance screening. Methods: We conducted a systematic review of the validity and utility of simulation modeling in CRC screening delivery (Chapter 1, 2). Next, a retrospective cohort study of CRC screening participation and outcomes between 2014-2019 was conducted (Chapter 3). We used this data and the findings of the systematic review to inform our participatory simulation modeling approach (Chapter 4). With end-users of the simulation model (clinicians, administrators, and patients), we revised an existing simulation model, OncoSim-CRC, to estimate the resource requirements and outcomes of various strategies to deliver a CRC screening program in the NWT. Each scenario model was run for 500 million cases and model validity was assessed. To enhance ongoing collaboration, we shared the concepts of a Communities of Practice (CoP) framework with stakeholders and assisted in generating consensus on priorities for a CoP to address (Chapter 5). Results: The systematic review showed that simulation models have been used to generate evidence critical to informing decision making for a broad range of decisions related to CRC screening delivery. However, the impact of these models on decision making, end-user engagement, and model validity were rarely described. In the retrospective cohort study, we observed that fecal immunohistochemical test(FIT)-based CRC screening did not appear to prevent CRC or provide earlier detection, but did result in more frequent positive pathology results than anticipated for average risk screening. Factors associated with this include long wait times for colonoscopy, over 1 in 3 FIT positive individuals had clinical signs and symptoms of CRC, and higher relative risk of advanced neoplasia among indigenous individuals. These findings and the involvement of end-users, informed the simulation model study. Under the parameters of the model, we estimate that colonoscopy demand with a CRC screening program would surpass capacity within 1-2 years, and continue to increase over the next 10-15 years due to adenoma surveillance. If this colonoscopy demand is met, we estimate screen detected cancers would increase by 110%, and clinically detected cases reduce by 26%. Increasing the phase-in period or revising adenoma follow-up guidelines would reduce demand and still improve cancer detection and prevention. A framework for a CoP, and consensus on priorities among stakeholders were established. Conclusion: Participatory simulation modeling was a useful method of informing CRC screening delivery in a remote northern population. The simulated scenarios provide decision-makers with strategies to enhance programmatic screening while conserving colonoscopy resources. The findings of this thesis helps to characterize the current outcomes of CRC screening in the NWT, and identifies opportunities to improve CRC screening effectiveness for a remote and, largely indigenous population.