This study reconceptualizes the drivers of armed conflict in the Red Sea–Horn of Africa (RSHoA) region through a systematic review of the literature from 1955 to 2025. Our findings suggest the limitations of additive or single-level analyses and propose an integrated, multi-layer framework that explains how conflict emerges from domestic, regional, and global interactions and aims. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our study synthesizes peer-reviewed articles, academic monographs, and primary source materials and identifies three interdependent clusters of structural conditions: (1) state failure and internal fragmentation; (2) external intervention and proxy warfare; and (3) competition over strategic resources. These factors operate through reinforcing mechanisms, where state fragility enables external intervention, which in turn reshapes domestic politics and intensifies fragmentation, while competition over strategic resources links local instability to broader geostrategic dynamics. These findings suggest that the interaction between economic interests and security imperatives within regional and global power competition is a key driver that sustains conflict dynamics over time. Although the specific dynamics may evolve, the underlying causal framework remains remarkably consistent. Building on these findings, we advance a Multi-Layer Causal Conflict Model (MLCCM) that explains how cross-level interactions generate both persistence and shifts in conflict systems. Grounded in the regional security literature of the Red Sea-Horn of Africa (RSHoA), our framework offers broader applicability to structurally embedded conflicts elsewhere and contributes to global security studies by clarifying how conflict processes are produced and sustained through multi-layer, dynamic power configurations.