The drug delivery systems have evolved significantly, driven by the goals of improving therapeutic efficacy, patient compliance, and minimizing adverse effects. Next-generation technologies offer promise in overcoming challenges associated with conventional methods, including limited bioavailability, poor solubility, and inadequate targeting. Controlled-release formulations have revolutionized treatment strategies since the 1950s, offering advantages such as precise drug release kinetics, improved solubility, and reduced toxicity. Integrating advancements in material science, nanotechnology, and biotechnology, modern systems aim to optimize drug release kinetics, enhance targeting efficiency, and minimize systemic toxicity. Active targeting and stimuli-responsive strategies further refine delivery precision, addressing off-target effects and upgrading therapeutic outcomes. Future advancements will focus on developing long-acting delivery technologies and integrating smart materials for stimuli-triggered release, aiming to achieve personalized therapeutic interventions. However, challenges such as scalability, regulatory compliance, and long-term safety profiles necessitate rigorous evaluation and interdisciplinary collaboration. This review explores recent advancements, discusses challenges, and outlines future directions in next-generation drug delivery systems, aiming to foster more effective, targeted, and patient-centric therapeutic interventions.