Mpox, a zoonotic disease re-emerging from animals to humans, poses a risk of evolving into a global pandemic due to its high infectivity and potential asymptomatic transmission. This study maps the structure and configuration of mpox-related discussions on Twitter/X, identifies key influencers and top hashtags, and analyzes public sentiment. Data were collected using NodeXL Pro from May 7, 2022, to January 15, 2023, with the keyword “Monkeypox” and visualized using Gephi. Social network analysis ranked nodes by betweenness centrality scores to highlight key communicators, and the YifanHu layout algorithm visualized the network. Influential users, source topics, and hashtags were identified, and sentiment analysis was conducted using Azure Machine Learning tools. The analysis identified 11,397 mpox-related tweets. The network structure resembled a community with diverse participants. Influential users included health and science journalists, writers, academics, medical doctors, and public figures. News media and organizational websites were the top information sources, emphasizing the need for accessible scientific information. “Monkeypox” and “Mpox” were the most prevalent hashtags. Negative sentiments dominated the discussion. This analysis provides insights into network structure, key influencers, information sources, and public sentiment, aiding tailored health initiatives to address misinformation and advocate valid health information and emergency responses.