Theaflavins (TFs), which are polyphenolic compounds characterized by a benzotropolone structure, serve as the primary quality and health-promoting components in black tea. Recent investigations have disclosed various health advantages linked to TFs, especially their potential to act as lead compounds in the formulation of therapeutic drugs targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), positioning them as a significant area of focus within food science and nutrition research. This review initially examines the primary physiological activities, mechanisms of action, and challenges related to TFs. It subsequently details the formation mechanism of enzyme-catalyzed TFs from catechins. Building upon this groundwork, this review assesses the recent advancements in two in vitro synthesis methods of TFs: enzymatic oxidation and nonenzymatic synthesis. Finally, the challenges that arise during the large-scale industrial implementation of these synthesis techniques are analyzed, and research strategies aimed at mitigating these issues are suggested. The primary goal of this review was to provide insightful perspectives and guidance for prospective research and industrial utilization of TFs.