Traditional drug delivery methods (tablets, capsules, syrups, ointments, etc.) are not able to produce sustained release and have low bioavailability along with changes in plasma drug level. The entire therapy process may be pointless in the absence of an effective delivery of the system. The drug must also be delivered at a precise target spot at a predetermined controlled pattern to achieve optimal efficacy and safety. Many aspects of therapeutic efficacy, like pharmacokinetics, distribution, absorption into cells and metabolism, excretion and clearance, and toxicity, are impacted by the route of delivery. Both innovative delivery systems and a greater understanding of the basic principles underlying how drug distribution influences safety and efficacy are required as the biotechnology sector develops novel kinds of biopharmaceuticals. Drug resistance is still an ongoing issue though, mostly owing to our incomplete knowledge of the biological barriers that prevent many drugs from reaching their intended targets. Despite the significant advantages of immunotherapy, off-target effects continue to cause serious adverse immune reactions. Recently, the research and development of drug delivery systems (DDS) have gained increased attention. Over decades of innovation, DDS has proven effective in delivering drugs with precision, thereby reducing side effects. They also offer benefits such as flexible control over drug release, improved pharmacokinetics, and enhanced drug distribution. Therefore, in this book chapter, a detailed overview of combining the approach of immunotherapies and vaccines with drug delivery systems is discussed to improve the therapeutic effect.