The widespread adoption of Unmanned Aerial Vehicles (UAVs) in civilian domains, such as airport security and critical infrastructure protection, has introduced significant safety risks that necessitate effective countermeasures. High-Energy Laser Systems (HELSs) offer a promising defensive solution; however, when confronting large-scale malicious UAV swarms, the Dynamic Resource Target Assignment (DRTA) problem becomes critical. To address the challenges of complex combinatorial optimization problems, a method combining precise physical models with multi-agent reinforcement learning (MARL) is proposed. Firstly, an environment-dependent HELS damage model was developed. This model integrates atmospheric transmission effects and thermal effects to precisely quantify the required irradiation time to achieve the desired damage effect on a target. This forms the foundation of the HELS–UAV–DRTA model, which employs a two-stage dynamic assignment structure designed to maximize the target priority and defense benefit. An innovative MADDPG-IA (I: intrinsic reward, and A: attention mechanism) algorithm is proposed to meet the MARL challenges in the HELS–UAV–DRTA problem: an attention mechanism compresses variable-length target states into fixed-size encodings, while a Random Network Distillation (RND)-based intrinsic reward module delivers dense rewards that alleviate the extreme reward sparsity. Large-scale scenario simulations (100 independent runs per scenario) involving 50 UAVs and 5 HELS across diverse environments demonstrate the method’s superiority, achieving mean damage rates of 99.65% ± 0.32% vs. 72.64% ± 3.21% (rural), 79.37% ± 2.15% vs. 51.29% ± 4.87% (desert), and 91.25% ± 1.78% vs. 67.38% ± 3.95% (coastal). The method autonomously evolved effective strategies such as delaying decision-making to await the optimal timing and cross-region coordination. The ablation and comparison experiments further confirm MADDPG-IA’s superior convergence, stability, and exploration capabilities. This work bridges the gap between complex mathematical and physical mechanisms and real-time collaborative decision optimization. It provides an innovative theoretical and methodological basis for public-security applications.