Ophiocordyceps sinensis, a fungus revered in traditional Asian medicine, is critically endangered due to climate change and overharvesting. Artificial cultivation is thus essential to meet demand and promote conservation. This review systematically analyses the decline of wild O. sinensis and evaluates the two primary cultivation strategies: in vitro mycelial fermentation and in vivo inoculation. We find that in vitro fermentation, while scalable and standardized, yields a chemical profile distinct from that of wild fungi. In vivo inoculation can produce fruiting bodies morphologically and chemically closer to wild specimens but is hampered by technical challenges in host rearing and low infection rates. By dissecting these bottlenecks, this review provides a framework for the sustainable cultivation of O. sinensis, crucial for preserving both a cornerstone of traditional medicine and the ecological balance of its native habitats.