A regional ozone (O3) pollution event occurred in the Yangtze River Delta region during August 17–23, 2020 (except on August 21). This study aims to understand the causes of O3 pollution during the event using an emission-based model (i.e., the Community Multiscale Air Quality (CMAQ) model) and an observation-based model (OBM). The OBM was used to investigate O3 sensitivity to its precursors during the O3 pollution, concluding that O3 formation was limited by volatile organic compounds (VOCs) on August 19, but was co-limited by VOCs and nitrogen oxides (NOx) on other polluted days. Aromatics and alkenes were the two main VOC groups contributing to the O3 formation, with trans-2-butene and m/p-xylene as the key species among the VOCs measured at the Nanjing urban site. The source apportionment results estimated using the source-oriented CMAQ model suggest that the transportation and industry sources dominated the non-background O3 production in Nanjing, which were responsible for 52% and 24.7%, respectively. The O3 concentration attributed to NOx (~70%) was significantly higher than that attributed to VOCs (approximately 30%). The process analysis revealed that vertical mixing increased the O3 concentrations in the early morning, and photochemical reactions promoted O3 formation and accumulation during the daytime within the planetary boundary layer. At night, outflow from horizontal transport and nocturnal chemistry jointly resulted the O3 depletion. The contributions of inter-city transport during the O3 pollution period in Nanjing were also estimated. The predicted O3 concentration was largely recorded from long-distance regions, reaching 46%, followed by local sources (38%) and surrounding cities (16%). The results indicate that both NOx and VOCs contributed significantly to O3 pollution during this event, and the emissions controls of NOx and the key VOC species of aromatics and alkenes from a cooperative regional perspective should be considered to mitigate O3 pollution.