Oxy-fuel circulating fluidized bed combustion is known as one of the most potent fuel combustion technologies that capture ultra-low greenhouse gases and pollutant emissions. While many investigations have been conducted for carbon capturing, the associated in-situ desulfurization process using calcium-based sorbents should also be underlined. This paper critically reviews the effects of changes in the operating environment on in-situ desulfurization processes compared to conventional air combustion. A comprehensive understanding of the process, encompassing hydrodynamic, physical and chemical aspects can be a guideline for designing the oxy-fuel combustion process with effective sulfur removal, potentially eliminating the need of a flue gas desulfurization unit. Results from thermogravimetric analyzers and morphological changes of calcium-based materials were presented to offer an insight into the sulfation mechanisms involved in the oxy-fuel circulating fluidized beds. Recently findings suggested that in-situ direct desulfurization is influenced not only by the desulfurization kinetics but also by the fluidization characteristics of calcium-based materials. Therefore, a complex reaction analysis that incorporated oxy-combustion reactions, computational fluid dynamics modeling, in-situ desulfurization reaction models and particle behavior can provide a thorough understanding of desulfurization processes across the reactor. Meanwhile, machine learning as a robust tool to predict desulfurization efficiency and improve operational flexibility should be applied with consideration of environmental improvement and economic feasibility.