Modern medicine has witnessed a continuous growth of different techniques in medication treatment. Transdermal drug delivery system (TDDS) offers a painless method of drug administration to a patient's skin. It has many advantages over other conventional drug routes, especially for self-administration patients and for long-term treatment medication. Microneedle technology is one of the methods being widely discovered as it provides minimally invasive skin. Painless experience has some benefits for skin permeability properties; thus, a variety of small molecules, proteins, and nanoparticles can pass through a skin layer. Microneedles have been effectively used to extract interstitial fluid (ISF) by various methods, and integrated microneedles in wearable monitoring and delivery devices provide real-time dose modification. These days, transdermal drug delivery methods are applied in a number of therapeutic domains, including the treatment of heart disease, motion sickness, hormone replacement, pain management, and quitting smoking. Drug potency is increased, and relative adverse effects are reduced using TDDS. An autoimmune condition that affects several systems is called systemic lupus erythematosus, or SLE. It triggers the activation of both innate and adaptive immunity that may involve only one organ or may affect the entire system. The current goals of SLE treatment are organ damage prevention, remission, and general quality of life enhancement. Therefore, in this chapter, the authors reviewed the possible severe illness of SLE monitoring using microneedle-based and current technology utilized for the treatment. It covers every major facet of the subject, such as material selection, design philosophy, operating mechanisms, and gadget utility.