Background: In the last decade, a varied prevalence of lifestyle-mediated health ailments ranging from infectious disorders to non-curable diseases has been observed. Globally the stone formation (lithiasis) in human kidneys has increased the trauma and economic burden. Furthermore, affordable rapid diagnosis, clinical trials, and therapeutics have to be addressed with newer holistic approaches. Objective: The current comprehensive review attempts to study kidney stones using emerging translational, conventional, and non-conventional research models, which include prokaryotic and eukaryotic systems (in vitro, semi-in vivo, and in vivo). Methods: The study eligibility criteria included systematic reviews and meta-analyses to explore various lithiatic models. Further, PubMed, PubMed Central, CINAHL Plus, Scopus, Web of Science, and EMBASE were used as data sources for the current study. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used. Results: All curated literature from past 55 years (1967–2022) were considered for this review with keywords as "Experimental models for human kidney stones" AND "Nephrolithasis" AND "Urolithasis". A total of 765 abstracts were reviewed for inclusion with 414 selected for full-text review. A total of 47 studies were analyzed. Mean AMSTAR score of 6.96/11 (± 1.84) suggests moderate quality of the systematic reviews. Conclusion: This review will empower clinicians, veterinarians, and researchers for a better understanding of the pathogenesis, causative factors, and prevalence of nephrolithiasis and urolithiasis and their associated mechanisms with rapid, reliable, and reproducible models. The findings of the study will aid in designing global healthcare policy and regional insurance for lithiatic disorders with effective therapeutics which will result in an increased quality of life, leading to better health and hygiene.