This review provides a comprehensive overview of the formation processes of calcareous nephrolithiasis, focusing on two distinct birthplaces: the renal interstitium and tubule lumen. Kidney stones, a common and burdensome condition, are primarily composed of calcium oxalate (CaOx) and calcium phosphate (CaP). The formation of these stones involves a complex, multi-step process influenced by physical, chemical, and biological factors. In the renal interstitium, calcified plaques (Randall's plaques) form in the basement membranes of the thin Henle loops, eventually breaking through the urothelium and serving as niduses for CaOx crystal growth. In the tubular lumen, crystal nucleation, growth, aggregation, and adhesion occur, leading to the formation of Randall's plugs, which block the openings of collecting ducts and promote stone growth. Key factors in the formation process include abnormal urine composition, oxidative stress, inflammation, and an imbalance of stone inhibitors and promoters. The review highlights the importance of understanding these mechanisms to develop more effective prevention and treatment strategies for kidney stone disease.This review provides a comprehensive overview of the formation processes of calcareous nephrolithiasis, focusing on two distinct birthplaces: the renal interstitium and tubule lumen. Kidney stones, a common and burdensome condition, are primarily composed of calcium oxalate (CaOx) and calcium phosphate (CaP). The formation of these stones involves a complex, multi-step process influenced by physical, chemical, and biological factors. In the renal interstitium, calcified plaques (Randall's plaques) form in the basement membranes of the thin Henle loops, eventually breaking through the urothelium and serving as niduses for CaOx crystal growth. In the tubular lumen, crystal nucleation, growth, aggregation, and adhesion occur, leading to the formation of Randall's plugs, which block the openings of collecting ducts and promote stone growth. Key factors in the formation process include abnormal urine composition, oxidative stress, inflammation, and an imbalance of stone inhibitors and promoters. The review highlights the importance of understanding these mechanisms to develop more effective prevention and treatment strategies for kidney stone disease.