The trends of urolithiasis have been immerged as noteworthy public health associated social and economic issue, specifically attributed towards the dietary and lifestyle habits. Strange aspects in the history of urolithiasis enlights modern and current changes in its epidemiology. The incidence and rate of urolithiasis exhibited as per the geographical variations which were associate with individual parameters including age, sex, dietary habit and genetic variations. It was found that, more than 15 % of population living in the developing area were victimized for nephrotic alteration in which different types of urinary calculi were prominently documented in early Ayurveda (Sanskrit literature ) during the period of between 3000 BC. to 2000 BC. Since then, problem of stone formation and related pathetic condition in human who has received challenge against medical sector with its multifunction etiology and high rate of recurrence. Crystallization found and reported because of imbalance between promoters and inhibitors. With respect to challenges in the field, there are number of inhibitors of crystal formation including molecules, peptides, proteins and biological derivatives came in to the focus. In general urolithiasis includes supersaturation, nucleation, aggregation and retention of urinary crystals within the nephrotic cells. Sequential steps were modulated by irregular metabolic and biochemical in the process crystallization. Typically, calcium cascade leads to activate undesired biochemical changes for crystallization, which cause cellular damage, along with non-recoverable alternations reported in historical literature. Acute and severe pains, necrotic inflammation and related biological alteration were imposed for pathophysiological and medical emergencies. In a modern era, comprehensive biological and metabolic assessment is crucial step towards diagnosis. Medical and therapeutic impact customize with respect to patients for effective management and limits further undesired damage and recurrence to save the life. To enhance therapeutic approaches, it is essential to gain in-depth knowledge about known facts, new drugs, upcoming techniques and different avenues to overcome the saturation, crystallization and aggregation in nephrotic cell to stop further kidney damage. As a future perspective, understanding of urolithiasis, pathophysiology, metabolism, alterations and drug delivery ending the story up to recovery in the kidney seems to be more challenged but demanding attention to understand smooth and socioeconomic potential of clinical work. To understand, investigate and come up with new trends in biological and clinical sciences to overcome the problem of urolithiasis in association with action of proactive drug, its impact and nature of biomechanics in the nephron, present review has been carried out