(), a significant contributor to the global challenge of antibiotic resistance, is not only a ubiquitous component of the human microbiome but also a potent pathogen capable of causing a spectrum of diseases. This review provides a thorough analysis of the intricate interactions between and the human immune system, elucidating its substantial impact on metabolic processes. We explore the mechanisms employed by to evade and manipulate immune responses, including molecular mimicry, immune modulation, and biofilm formation. The review further investigates the bacteriums influence on metabolic pathways, particularly glycolysis, highlighting how these interactions exacerbate disease severity. The emergence of multidrug-resistant and extremely drug-resistant strains within the Enterobacteriaceae family has heightened the public health crisis, underscoring the urgency for comprehensive research. We investigate the roles of the host's complement system, autophagy, cell death mechanisms, and various cytokines in combating infections, shedding light on areas that warrant further academic investigation. Additionally, the review discusses the challenges posed by K1- and K2-capsule polysaccharides in vaccine development due to their complex molecular structures and adhesive properties. Acknowledging the limited availability of effective antimicrobials, this review advocates for exploring alternative approaches such as immunotherapeutics, vaccinations, and phage therapy. We consolidate current knowledge on , covering classical and non-classical subtypes, antimicrobial resistance-mediated genes, virulence factors, and epidemiological trends in isolation and antibiotic resistance rates. This comprehensive review not only advances our understanding of but also underscores the imperative for ongoing research and collaborative efforts to develop new prevention and treatment strategies against this formidable pathogen.