Time-sequenced drug release, or sequential drug release, represents a pivotal strategy in the synergistic treatment of diseases using nanocomposites. Achieving this requires the rational integration of multiple therapeutic agents within a single nanocomposite, coupled with precise time-controlled release mechanisms. These nanocomposites offer many advantages, including enhanced therapeutic synergy, reduced side effects, attenuated adverse interactions, improved stability and optimized drug utilization. Consequently, research in the field of drug delivery and synergistic therapy has become increasingly important. Currently, sequential drug release research is still in the data collection and basic research stages, and its potential has not yet been fully explored. Although prior studies have explored the sequential drug release strategy in various contexts, a comprehensive review of the underlying mechanisms and their applications in nanocomposites remains scarce. This review categorizes different types of sequential drug release strategies and summarizes diverse nanocomposites, focusing on both physical approaches driven by structural variations and chemical methods based on stimulus-responsive mechanisms. Furthermore, we highlight the major applications of sequential drug release strategies in the treatment of various diseases and detail their therapeutic efficacy. Finally, emerging trends and challenges in advancing sequential drug release strategies based on nanocomposites for disease treatment are also discussed.