Stem cell transplantation has become a cornerstone in the treatment of hematologic malignancies and various genetic disorders, with posttransplant monitoring playing a vital role in predicting clinical outcomes. Chimerism analysis enables the assessment of donor-recipient cell dynamics and serves as an essential indicator for engraftment success, risk of relapse, and graft-versus-host disease (GVHD). Recent technological advances have significantly enhanced the sensitivity, specificity, and clinical applicability of chimerism detection. Among these, next-generation sequencing (NGS) has transformed molecular monitoring by providing high-resolution characterization of mixed chimerism, while digital droplet polymerase chain reaction (ddPCR) offers robust quantification of low-level residual recipient cells. In addition, emerging single-cell and epigenetic profiling approaches hold promising potential for identifying early immune reconstitution patterns and relapse-associated minimal residual disease (MRD). This abstract highlights the evolution of chimerism assays from conventional short tandem repeat (STR)-based techniques toward precision-driven molecular platforms and emphasizes the importance of integrating novel analytical tools into clinical transplantation practice. Continuous innovation in chimerism monitoring will enable earlier intervention and improved long-term outcomes for stem cell transplant recipients.