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Doxorubicin (DOX)-based chemotherapy for breast cancer is frequently compromised by systemic toxicity, poor tumor selectivity, and multidrug resistance, underscoring the need for localized and multimodal therapeutic strategies. Here, we developed an injectable peptide–gold–drug (PAD) conjugate-integrated photocrosslinked methacry-loyl hyaluronic acid (HAMA/PAD) hydrogel that couples stimuli-responsive chemotherapy with NIR-triggered photothermal therapy in a single platform. Two-dimensional peptide nanosheets (PNSs) self-assembled from Fmoc-FKKGSHC served as multifunctional molecular scaffolds for the spatial organization of gold nanoparticles (AuNPs) and thiolated DOX (DOX-SH) through Au–S coordination, generating PAD conjugates. This hierarchical nano-to-macro integration enables the HAMA/PAD hydrogel to function simultaneously as an injectable depot and a localized tumor microenvironment. The resulting HAMA/PAD hydrogel exhibited an interconnected porous architecture, shear-thinning behaviour, compatible with syringe-based delivery prior to photocrosslinking, and a storage modulus of approximately 100 Pa. Importantly, PAD exhibited efficient DOX incorporation, while the hydrogel provided pH- and glutathione (GSH)-responsive drug release, offering stimuli-dependent control over DOX availability. Under 808 nm NIR irradiation, HAMA/PAD rapidly generated localized hyperthermia, reaching approximately 55 °C, and maintained stable photothermal performance over repeated irradiation cycles. Additionally, the hydrogel exhibited good cytocompatibility toward L929 fibroblasts, whereas combined HAMA/PAD and NIR treatment reduced 4T1 breast cancer cell viability to approximately 10%, demonstrating a pronounced chemo-photothermal effect. Overall, this study establishes a PNS-enabled strategy for integrating nanoscale drug/photothermal components within an injectable hydrogel depot, providing a versatile platform for localized, stimulus-responsive, and combined chemo-photothermal treatment.