The management of nuclear waste, characterized by its long-lasting radioactivity and environmental risks, calls for innovative remediation strategies. Traditional disposal methods have proven inadequate, compelling exploration into alternative approaches. Among these, microbial bioremediation has emerged as a promising, eco-friendly strategy to mitigate the extensive impact of nuclear waste. Microorganisms, spanning bacteria, archaea, and fungi, exhibit remarkable capabilities in interacting with various forms of nuclear waste, including radionuclides, heavy metals, and organic contaminants. Leveraging mechanisms like bioaccumulation, biotransformation, and biomineralization, these microorganisms effectively immobilize or detoxify hazardous elements. Certain microbial species thrive in extreme conditions, such as environments characterized by elevated radiation levels and hostile pH conditions, aligning their utility with the demands of nuclear waste repositories. Recent advances in microbial genetics and metabolic pathway elucidation have significantly enhanced the precision and efficiency of bioremediation techniques. Microbial bioremediation offers environmental and economic advantages over conventional methods, mitigating long-term risks. This chapter underscore the pivotal role of microorganisms in nuclear waste bioremediation, presenting a responsible, cost-effective solution to a pressing challenge of the nuclear age. Ongoing research in microbial bioremediation promises to further enhance the field, ultimately contributing to the development of safer, more efficient strategies for nuclear waste management.