Targeted polymeric therapeutic nanoparticles have evolved from traditional biodegradable materials to multifunctional nanoparticles capable of targeted delivery and controlled release of drugs and diagnostics. These nanoparticles are engineered to navigate the complex in vivo environment, enabling precise targeting and optimal drug delivery at the tissue, cell, and subcellular levels. This optimization enhances drug safety and efficacy, potentially complementing traditional drug enhancements through medicinal chemistry. Polymeric nanoparticles offer a new class of therapeutics distinct from conventional drugs and first-generation nanoparticles, with the potential to significantly improve clinical outcomes through optimized drug delivery. Polymeric nanoparticles have shown promise in various applications, including improved drug solubility, metabolism, and biodistribution, as well as enhanced therapeutic efficacy through targeted delivery. They can deliver multiple types of therapeutics, including imaging and therapeutic agents, enabling real-time monitoring of treatment effectiveness. The combination of optimally designed drugs with engineered polymeric nanoparticles can lead to highly differentiated therapeutics with improved safety and efficacy. Controlled release polymeric nanoparticles have been developed to address the limitations of lipid-based nanoparticles, such as liposomes, which often exhibit poor stability and limited drug loading capacity. Polymeric nanoparticles offer superior stability, high drug loading, and the ability to control drug release kinetics. These properties make them well-suited for a wide range of medical applications, including oncology, where they can enhance drug delivery to tumour sites through passive targeting mechanisms like the enhanced permeation and retention (EPR) effect. Passive targeting relies on the EPR effect, which allows nanoparticles to accumulate in tumour tissues due to the abnormal vasculature of tumours. However, challenges such as tumour heterogeneity and interstitial pressure can limit the effectiveness of passive targeting. Active targeting, on the other hand, involves the use of affinity ligands to direct nanoparticles to specific disease sites, enhancing cellular uptake and therapeutic efficacy. Examples of actively targeted nanoparticles include those conjugated with antibodies, peptides, or other ligands that recognize overexpressed antigens on cancer cells. Despite the potential of polymeric nanoparticles, challenges remain in their clinical translation, including issues related to nanoparticle synthesis, biocompatibility, and immune responses. However, ongoing research and development are addressing these challenges, with several polymeric nanoparticles currently in clinical trials. These include BIND-014, a prostate-specific membrane antigen-targeted nanoparticle, and CALAA-01, a nanoparticle designed for siRNA delivery. These developments highlight the growing importance of polymeric nanoparticles in the field of nanomedicine and their potential to revolutionize therapeutic approaches.Targeted polymeric therapeutic nanoparticles have evolved from traditional biodegradable materials to multifunctional nanoparticles capable of targeted delivery and controlled release of drugs and diagnostics. These nanoparticles are engineered to navigate the complex in vivo environment, enabling precise targeting and optimal drug delivery at the tissue, cell, and subcellular levels. This optimization enhances drug safety and efficacy, potentially complementing traditional drug enhancements through medicinal chemistry. Polymeric nanoparticles offer a new class of therapeutics distinct from conventional drugs and first-generation nanoparticles, with the potential to significantly improve clinical outcomes through optimized drug delivery. Polymeric nanoparticles have shown promise in various applications, including improved drug solubility, metabolism, and biodistribution, as well as enhanced therapeutic efficacy through targeted delivery. They can deliver multiple types of therapeutics, including imaging and therapeutic agents, enabling real-time monitoring of treatment effectiveness. The combination of optimally designed drugs with engineered polymeric nanoparticles can lead to highly differentiated therapeutics with improved safety and efficacy. Controlled release polymeric nanoparticles have been developed to address the limitations of lipid-based nanoparticles, such as liposomes, which often exhibit poor stability and limited drug loading capacity. Polymeric nanoparticles offer superior stability, high drug loading, and the ability to control drug release kinetics. These properties make them well-suited for a wide range of medical applications, including oncology, where they can enhance drug delivery to tumour sites through passive targeting mechanisms like the enhanced permeation and retention (EPR) effect. Passive targeting relies on the EPR effect, which allows nanoparticles to accumulate in tumour tissues due to the abnormal vasculature of tumours. However, challenges such as tumour heterogeneity and interstitial pressure can limit the effectiveness of passive targeting. Active targeting, on the other hand, involves the use of affinity ligands to direct nanoparticles to specific disease sites, enhancing cellular uptake and therapeutic efficacy. Examples of actively targeted nanoparticles include those conjugated with antibodies, peptides, or other ligands that recognize overexpressed antigens on cancer cells. Despite the potential of polymeric nanoparticles, challenges remain in their clinical translation, including issues related to nanoparticle synthesis, biocompatibility, and immune responses. However, ongoing research and development are addressing these challenges, with several polymeric nanoparticles currently in clinical trials. These include BIND-014, a prostate-specific membrane antigen-targeted nanoparticle, and CALAA-01, a nanoparticle designed for siRNA delivery. These developments highlight the growing importance of polymeric nanoparticles in the field of nanomedicine and their potential to revolutionize therapeutic approaches.