Public health agencies (PHAs) have increasingly incorporated social media into their communication mix during successive pandemics in the 21st century. However, the quality, timing, and accuracy of their health messages have varied significantly, resulting in mixed outcomes for communication, audience engagement, and pandemic management. This study aimed to identify factors influencing the effectiveness of pandemic-related health messages shared by PHAs on social media and to report their impact on public engagement as documented in the literature. A scoping literature review was conducted following a predefined protocol. An electronic search of 7 relevant databases and 5 grey literature repositories yielded 9,714 papers published between January 2003 and November 2022. Seventy-three papers were deemed eligible and selected for review. The results underscored the insufficiency of social media guidance policies for PHAs. Six themes were identified: message source, message topic, message style, message timing, content credibility and reliability, and message recipient profile. These themes encompassed 20 variables that could inform PHAs’ social media public health communication during pandemics. Additionally, the findings revealed potential interconnectedness among the variables, and this study concluded by proposing a conceptual model that expands upon existing theoretical foundations for developing and evaluating pandemic-related health messaging.