The objective of this study is to assess the impact of spray drying conditions on medium-chain triglyceride (MCT) loading, solubility, and release of an MCT-loaded solid self-emulsifying system in a water-insoluble oily substance. MCT-loaded solid self-emulsifying systems are prepared by spray drying with SDS and calcium silicate. The effects of inlet temperature (60, 80, or 100oC) and feed solution composition (0, 10, 50, 90, or 100% ethanol) on physicochemical properties of MCT-loaded solid self-emulsifying systems are studied. The inlet temperature significantly affects the water solubility of MCT. Moreover, the feed solution composition significantly affects water solubility, release rate, and MCT loading. The MCT-loaded solid self-emulsifying system obtained at 60oC using 90% ethanol feed solution shows the best physicochemical properties among the synthesized products and exhibits better water solubility (4.43 ± 0.44 vs. 0 μg/mL) and release (94.4 ± 1.6 vs. 32.8 ± 7.4%, 60 min) than a commercial product. Furthermore, the MCT-loaded solid self-emulsifying system shows an excellent emulsion droplet size (approximately 230 nm).