Urolithiasis represents one of the most common urologic diseases, and its incidence demonstrates, globally, an increasing trend. The application of preventive measures is an established strategy to reduce urolithiasis-related morbidity, and it is based mostly on the adaptation of lifestyle factors and pharmacotherapy. Furthermore, other research areas demonstrate promising results, such as the research on the microbiome. In the current review, we searched for the latest data on lifestyle-based prevention and microbiome alterations in urolithiasis patients. The majority of the proposed lifestyle measures are already included in the urological guidelines, while additional factors, such as vitamin D supplementation, seem to have a putative positive effect. From the microbiome studies, several microbial composition patterns and metabolic pathways demonstrated an inhibiting or promoting role in lithogenesis. Up to the present, stone prevention has not shown satisfying results, which suggests that lifestyle measures are not adequate. Moreover, microbiome studies are prone to bias, since microbes are strongly affected by numerous clinical factors, while the analysis procedures are not standardized yet. Analysis standardization and data pooling from extensive registration of clinical and microbiome data are essential steps in order to improve the existing prevention strategy with targeted microbiome manipulations.