This research proposes guidelines for hypothesizing and assessing mediation concepts for tourism and hospitality research. The mediation analysis plays a significant role in theory development and advancement in social science disciplines and is significantly increasing in recent years. However, following questionable hypothesis development, statistical assessment, and interpretation of results cause biased and unreliable understanding of mediation analysis and questionable findings for theory building and development. Drawing from a systematic review of 536 mediation papers published in five recent years (2016–2020) in top tier tourism and hospitality journals, the findings revealed several critical issues in different mediation analysis steps, including hypothesis development, mediation assessment and interpretation of results. The results highlighted the common methodological mistakes and misconceptions for mediation analysis. This paper provides robust guidelines for mediation analysis by highlighting those methodological issues and has significant theoretical and methodological contributions in the tourism and hospitality field.