The semen microbiome, once believed to be sterile, is now recognized as a dynamic ecosystem containing a diverse range of microorganisms with potential implications for male fertility and reproductive health. We aimed to examine the relationship between the semen microbiome, male infertility, and reproductive outcomes, highlighting the transformative role of next generation sequencing techniques and bioinformatics in exploring this intricate interaction, and we present a critical review of the published literature on this issue. Current evidence suggests a complex association between the composition of the semen microbiome and male fertility, with certain bacterial genera, such as Lactobacillus and Prevotella that exert opposing effects on sperm quality and DNA integrity. In addition, the influence of the semen microbiome extends beyond natural fertility, affecting assisted reproductive technologies and pregnancy outcomes. Despite considerable progress, challenges remain in standardizing methodologies and interpreting findings. In conclusion, we identify the lack of a definitive management proposal for couples presenting with this phenomenon, and we underline the need for an algorithm and indicate the questions raised that point toward our goal for a strategy. Continued research is essential to clarify the role of the semen microbiome in male reproductive health and to advance the development of personalized fertility management approaches.