Helicobacter pylori infection is the most prevalent cause of gastric adenocarcinoma. In prospective population-based research, a significant link to cancer risk in East Asia with seropositivity to the unspecified H. pylori proteins Hp0305 and Hp1564 was found. Yet, there has been no explanation for the mechanism behind this finding. As previously identified, H. pylori’s capable to collaborate with Hp0305 and Hp1564 and virulence pathways to bring about cellular changes that drive gastric tumor growth. It was observed that there was increased gastric atrophy across all gastric diseases in 546 patients with premalignant gastric abnormalities who were seropositive to Hp0305 and Hp1564. Levels of gastric cell-associated bacteria were reduced significantly by in vitro Hp0305 and Hp1564 depletion, with the capacity of H. pylori to stimulate pro-inflammatory cytokine production being severely curtailed. Hp1564 is essential for oncoprotein CagA movement into gastric epithelial cells, according to this research. The studies identify the molecular mechanisms underlying new H. pylori pathogenicity factors that are strongly linked to stomach illness and the potential of Hp0305 and Hp1564 as powerful molecular tools, which may be used to identify people who are highly susceptible to stomach cancer. Hp1564 and Hp0305 enhance inflammation and gastric cancer risk by promoting key bacterial-gastric cell interactions that facilitate the delivery of oncogenic macrobiotic cargo to target cells. As a result, Hp0305/Hp1564 prompts microbial interactions that may be therapeutically targeted to avoid the development of gastric cancer in high-risk people.