YouTube and TikTok have gained increasing recognition as social network sites to support online knowledge acquisition, sharing, and application via social media platforms in the medical field. This study examines which aspect of TikTok and YouTube stimulates doctors, nurses, and any other YouTube and TikTok in the medical setting, to rely on them as sources of knowledge acquisition and sharing to keep their medical repertoire updated. A hybrid model is designed to investigate users’ acceptance of YouTube and TikTok as social media platforms. The model focuses on four main external factors: Content richness, innovativeness, satisfaction, and enjoyment. These factors are connected with two TAM constructs which are perceived ease of use and perceived usefulness. The results have shown that both YouTube and TikTok are affected by PEOU, PU, personal innovativeness, flow theory, and content richness. Both social media networks provide up-to-date sources described as useful, enjoyable, and relevant. Nevertheless, the comparative results have shown that YouTube has deeply influenced users’ medical perception and knowledge compared to TikTok. It is created for the very mere purpose of socialization and self-expression. In contrast, YouTube is used for educational and non-educational purposes due to the type of uploaded content and time management. Therefore, TikTok developers and influencers should initiate highly specialized videos and create content that raises awareness of medical field issues.