Nanoparticles (NPs) are being engineered to improve drug delivery and precision medicine. This review discusses advanced NP designs for both non-personalized and precision applications, focusing on overcoming heterogeneous biological barriers to delivery. NPs can be lipid-based, polymeric, or inorganic, and are being optimized for personalized drug delivery. The review highlights the importance of understanding biological barriers and patient heterogeneity to improve NP design and clinical outcomes. NPs have the potential to enhance drug stability, solubility, and delivery efficiency. However, challenges remain in translating NP-based therapies to clinical practice due to issues such as biodistribution, clearance, and toxicity. The review also discusses the role of NP characteristics in determining their distribution and delivery, as well as the impact of patient-specific factors on NP performance. The review emphasizes the need for tailored NP designs that can overcome biological barriers and improve patient outcomes in precision medicine. NPs are being explored for various applications, including cancer therapy, immunotherapy, and in vivo gene editing. The review highlights the importance of understanding NP characteristics, such as size, shape, surface charge, and surface modifications, in optimizing their performance. The review also discusses the challenges of NP delivery in different biological environments, including the blood-brain barrier, gastrointestinal tract, and tumour microenvironment. Overall, the review underscores the potential of NPs in advancing precision medicine and improving therapeutic outcomes through tailored NP designs.Nanoparticles (NPs) are being engineered to improve drug delivery and precision medicine. This review discusses advanced NP designs for both non-personalized and precision applications, focusing on overcoming heterogeneous biological barriers to delivery. NPs can be lipid-based, polymeric, or inorganic, and are being optimized for personalized drug delivery. The review highlights the importance of understanding biological barriers and patient heterogeneity to improve NP design and clinical outcomes. NPs have the potential to enhance drug stability, solubility, and delivery efficiency. However, challenges remain in translating NP-based therapies to clinical practice due to issues such as biodistribution, clearance, and toxicity. The review also discusses the role of NP characteristics in determining their distribution and delivery, as well as the impact of patient-specific factors on NP performance. The review emphasizes the need for tailored NP designs that can overcome biological barriers and improve patient outcomes in precision medicine. NPs are being explored for various applications, including cancer therapy, immunotherapy, and in vivo gene editing. The review highlights the importance of understanding NP characteristics, such as size, shape, surface charge, and surface modifications, in optimizing their performance. The review also discusses the challenges of NP delivery in different biological environments, including the blood-brain barrier, gastrointestinal tract, and tumour microenvironment. Overall, the review underscores the potential of NPs in advancing precision medicine and improving therapeutic outcomes through tailored NP designs.