Kidney stone disease is a complex disorder with high heritability and prevalence. Previous genome-wide association studies (GWASs) have identified 21 susceptibility loci, while the mechanism involved in stones formation was still poorly understood. In this study, we performed the largest GWAS meta-analysis for kidney stones including 720,199 individuals (up to 17,969 cases) by combining UK biobank and FinnGen study. We have identified 44 susceptibility loci, including 28 novel loci, of which 23 were validated in Japanese population. Tissue and cell type-specific analysis pinpointed the proximal tubule which is responsible for the majority of calcium reabsorption as the key target cell type for kidney stones. By integrating kidney specific omics data, we applied three different strategies to prioritize 223 candidate genes, which strengthened the importance of ion homeostasis in stones formation and suggested potential target drugs for the treatment. The genitourinary and digestive diseases had larger genetic correlations with kidney stones, highlighting the comorbidity in the genitourinary system and gut-kidney axis. Our findings generated an atlas of candidate genes, tissue and cell types, pathways involved in the formation of kidney stones. Moreover, the study also provided the potential drug targets for the treatment of kidney stones and insights of shared regulation with other diseases.