Delivering chemotherapy at home or in mobile chemotherapy units has become increasingly popular due to its convenience and patient-centered approach. However, the high demand, complexity, and stochasticity of the Outpatient Chemotherapy Process (OCP) can lead to inefficiencies in implementing these services. To address this gap in the literature, this study presents a decision support framework and operational model for optimizing the OCP with the inclusion of home-based and mobile chemotherapy services. Data-driven research and relevant literature have been integrated to formulate the decision-making process in the proposed decision support framework. A mathematical model is developed to determine the patient and nurse assignments to outpatient department, home, or mobile chemotherapy services, as well as appointment scheduling. A discrete event simulation model is employed to solve the proposed model and determine the performance measures. The optimization experiment included various demand scenarios, and the results showed the value of implementing home-based and mobile chemotherapy services on patient waiting time and staff overtime under all the considered scenarios compared to a baseline. Finally, implementation and modeling strategies have been proposed for scholars and decision-makers to build on this work and benefit from its findings.