Abstract: At 00:17 Beijing Time on January 21, 2025, a magnitude 6.2 earthquake struck Tainan City, Taiwan Province, with the epicenter located at 23.24°N latitude and 120.51°E longitude, and a focal depth of 10 km. The earthquake reached a maximum intensity of IX on the Modified Mercalli Intensity scale, with the most severely affected areas concentrated in Chiayi County and Tainan City. However, overall seismic damage was relatively moderate. The observed impacts included partial collapse or severe damage to some buildings, with structural damage primarily affecting beam-column components. Non-structural damage was mainly observed in decorative materials, infill walls, and suspended ceilings. Within the lifeline infrastructure, bridges sustained only minor damage, predominantly in the form of abutment deformation, while road damage was characterized mainly by surface uplift and cracking. Secondary disasters included fires, power outages, and widespread landslides, the latter of which caused disruption to lifeline facilities and transportation networks. Post-earthquake damage assessments indicated that the primary causes of destruction were high ground motion intensity, substandard building quality, and insufficient seismic mitigation measures. A comparative analysis with the 2016 magnitude 6.6 Meinong earthquake in Kaohsiung revealed that the latter resulted in more severe damage, and the contributing factors are discussed in detail. Furthermore, this study evaluates the performance of the earthquake loss assessment models developed by the United States Geological Survey and our research team. The findings show that the USGS’s preliminary economic loss estimates were conservative, and its casualty assessments lacked clarity, whereas the model developed by our team demonstrated higher accuracy in both respects.