Mesenchymal stem cells (MSCs) have newly developed as a potential drug delivery system. MSC-based drug delivery systems (MSCs-DDS) have made significant strides in the treatment of several illnesses, as shown by a plethora of research. However, as this area of research rapidly develops, several issues with this delivery technique have emerged, most often as a result of its intrinsic limits. To increase the effectiveness and security of this system, several cutting-edge technologies are being developed concurrently. However, the advancement of MSC applicability in clinical practice is severely hampered by the absence of standardized methodologies for assessing cell safety, effectiveness, and biodistribution. In this work, the biodistribution and systemic safety of MSCs are highlighted as we assess the status of MSC-based cell therapy at this time. We also examine the underlying mechanisms of MSCs to better understand the risks of tumor initiation and propagation. Methods for MSC biodistribution are explored, as well as the pharmacokinetics and pharmacodynamics of cell therapies. We also highlight various promising technologies, such as nanotechnology, genome engineering technology, and biomimetic technology, to enhance MSC-DDS. For statistical analysis, we used analysis of variance (ANOVA), Kaplan Meier, and log-rank tests. In this work, we created a shared DDS medication distribution network using an extended enhanced optimization approach called enhanced particle swarm optimization (E-PSO). To identify the considerable untapped potential and highlight promising future research paths, we highlight the use of MSCs in gene delivery and medication, also membrane-coated MSC nanoparticles, for treatment and drug delivery.