Season 1 of Big White Duel is set against the backdrop of Ming Shing North Hospital, the largest public hospital in Hong Kong. The story centers on healthcare system reform and the ideological conflicts among medical professionals. The plot follows the newly appointed Deputy Hospital Chief, Dr. Yeung Yat-to (played by Roger Kwok), as he advocates for the implementation of a "universal healthcare scheme." Through this, the series explores the ethical dilemmas, power struggles, and moral choices brought about by institutional change. A series of intense medical incidents and emergency cases further highlights the constant struggle doctors face between professional duty, political intrigue, and personal emotion.

With CE Yeung Yat-to and Deputy CE Tong Ming at the helm of the leading public health institution Marshall Paxton Hospital, core departments, namely neurosurgery, CTS and A&E, are writing life-saving medical stories. The failed medical reform plan had not in any way frustrated Yat-to, who puts forward Comprehensive Opening Up of the Drug Formulary Bill with the aim of providing low-cost medications to rare disease patients. However, oncologist Ip Ching objects to his proposal, and she even goes against Yat-to as she is appointed as MarsPax CE. Meanwhile, former W.M.U. member Lee Man-shun joins the MarsPax team and collaborates with A&E Dr Zoe So, neurosurgeon Lui Oi-ling and other white knights in handling all kinds of critical situations.