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 100°C) 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 60°C 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).