Hypervirulent Klebsiella pneumoniae (hvKP), especially multidrug-resistant hvKP (MDR-hvKP) infections, are distributed globally, and lead to several outbreaks with high pathogenicity and mortality in immunocompetent individuals. This is usually characterized by a rapidly metastatic spread resulting in multiple pyogenic tissue abscesses. To date, even though the explanation of hypervirulent factors of hvKP has been identified, it still remains to be fully understood. The most common key virulence agents of hvKP included (1) siderophore systems for iron acquisition, (2) increased capsule production, (3) the colibactin toxin, (4) hypermucoviscosity, and so on. Several hypervirulence factors have been renewed, and the evolution of MDR-hvKP has been deeply explored recently. We aim to describe a chain of key virulence agents attributed to the lethality of hvKP and MDR-hvKP. In this review, recent advances in renewed factors in hypervirulence were summarized, and potential therapeutic targets are explored. Novel co-existence of hypervirulence agents and multidrug-resistant elements, even the superplasmid, was screened. Superplasmid simultaneously harbours hypervirulence and multidrug-resistant genes and can mobile autonomously by its complete conjugative elements. Research into related immunity has also gained traction, which may cause multiple invasive infections with higher mortality rates than classical ones, such as neutrophil- and complement-mediated activity. The evolution of virulence and multidrug resistance is accelerating. More reliable methods for identifying hvKP or MDR-hvKP must be investigated. Furthermore, it is critical to investigate innovative treatment targets in the future.