This review project aims to provide a biotechnological solution to the growing issue of antibiotic resistance encountered by astronauts during space missions. Due to stress factors such as microgravity and radiation in space, bacteria tend to mutate rapidly and develop resistance to conventional antibiotics. The central research question of this study is: “Can nisin, genetically modified using CRISPR-Cas9 technology, be transformed into a more effective, stable, and broad-spectrum antibacterial agent against antibiotic-resistant bacteria encountered in space conditions?” Within this review, the antimicrobial efficacy of genetically modified nisin variants is examined through a comparative analysis with conventional nisin and other natural antibacterial agents reported in the literature. The core hypothesis of the study is that genetically engineered nisin will demonstrate enhanced antibacterial efficacy and stability under space-like conditions when compared to traditional forms. While the antimicrobial applications of nisin in the food industry are well-established, there remains a significant gap in the literature regarding its performance under extreme conditions such as those in space. Therefore, this study not only contributes to space biotechnology but also to the development of next-generation therapeutic strategies against the global rise of antibiotic resistance. Additionally, the proposed approach offers a strategic innovation that can be integrated across disciplines including biotechnology, pharmaceutical sciences, microbiology, and space biology. The increasing need for biologically-based and genetically enhanced antimicrobial agents for infection control and immune support during long-term space missions makes this investigation highly relevant. Accordingly, it is anticipated that CRISPR-programmed nisin may serve as a safe and effective agent in both space-based and terrestrial medical applications.