Urolithiasis, or kidney stones, has emerged as a significant public health concern. Despite this, effective treatments targeting stone formation and recurrence are limited. This review delves into the molecular mechanisms underlying the condition. Investigating these molecular aspects can address existing gaps in treatment options. Future research can uncover new therapeutic strategies by targeting downstream pathways, and effector molecules. Cell signaling pathways offer potential targets, as they involve complex interactions that can be modulated to address multiple clinical symptoms. An imbalance in calcium and oxalate levels can lead to kidney stone formation which is characterized by oxidative stress, inflammation, and cell death. The interplay between key organelles like the endoplasmic reticulum and mitochondria triggers stress pathways, including oxidative stress and apoptosis. This review consolidates recent advances in understanding the pathophysiology and signaling events associated with kidney stones.