BACKGROUND: Social media has changed the communication landscape, exposing individuals to an ever-growing amount of information while also allowing them to create and share content. Although vaccine skepticism is not new, social media has amplified public concerns and facilitated their spread globally. Multiple studies have been conducted to monitor vaccination discussions on social media. However, there is currently insufficient evidence on the best methods to perform social media monitoring. OBJECTIVE: The aim of this study was to identify the methods most commonly used for monitoring vaccination-related topics on different social media platforms, along with their effectiveness and limitations. METHODS: A systematic scoping review was conducted by applying a comprehensive search strategy to multiple databases in December 2018. The articles' titles, abstracts, and full texts were screened by two reviewers using inclusion and exclusion criteria. After data extraction, a descriptive analysis was performed to summarize the methods used to monitor and analyze social media, including data extraction tools; ethical considerations; search strategies; periods monitored; geolocalization of content; and sentiments, content, and reach analyses. RESULTS: This review identified 86 articles on social media monitoring of vaccination, most of which were published after 2015. Although 35 out of the 86 studies used manual browser search tools to collect data from social media, this was time-consuming and only allowed for the analysis of small samples compared to social media application program interfaces or automated monitoring tools. Although simple search strategies were considered less precise, only 10 out of the 86 studies used comprehensive lists of keywords (eg, with hashtags or words related to specific events or concerns). Partly due to privacy settings, geolocalization of data was extremely difficult to obtain, limiting the possibility of performing country-specific analyses. Finally, 20 out of the 86 studies performed trend or content analyses, whereas most of the studies (70%, 60/86) analyzed sentiments toward vaccination. Automated sentiment analyses, performed using leverage, supervised machine learning, or automated software, were fast and provided strong and accurate results. Most studies focused on negative (n=33) and positive (n=31) sentiments toward vaccination, and may have failed to capture the nuances and complexity of emotions around vaccination. Finally, 49 out of the 86 studies determined the reach of social media posts by looking at numbers of followers and engagement (eg, retweets, shares, likes). CONCLUSIONS: Social media monitoring still constitutes a new means to research and understand public sentiments around vaccination. A wide range of methods are currently used by researchers. Future research should focus on evaluating these methods to offer more evidence and support the development of social media monitoring as a valuable research design.