Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies to tackle bacterial infections. Aside from developing new antibacterial compounds, microscale drug delivery systems have shown great potential for improving the efficacy of antibiotic therapies by providing localised and controllable drug release. Herein, various hierarchical microparticle systems were developed for triggerable multi-drug release of a variety of cargoes. A sequential dual delivery system was demonstrated using photo-responsive and enzyme-responsive core-shell microparticles composed of a mesoporous silica microparticle coated with stimuli-responsive peptide-crosslinked polymer shells. These particles were assembled into an autonomous cascade for the release of multiple model protein cargoes, activated by a UV light trigger. A second stimuli-responsive microparticle system was then developed to achieve simultaneous bacteria-activated dual antibiotic drug delivery for treating Gram-positive bacterial infections. Here, a capsosome system was designed, which consisted of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic-loaded liposomes. The capsosomes were engineered to release their drug payloads from the liposomes in the presence of methicillin-resistant Staphylococcus aureus (MRSA) toxins. MRSA-activated single drug delivery of vancomycin, as well as a synergistic dual delivery of vancomycin and an antibacterial peptide, was then demonstrated to effectively kill MRSA in vitro. Additionally, the in vivo bactericidal efficacy of these microparticles was further demonstrated in a Drosophila melanogaster MRSA infection model. Finally, preliminary studies were carried out to adapt the capsosomes for treating Gram-negative infections, which can be challenging due to the impermeable outer membrane of Gram-negative bacteria. Various approaches were trialled including the use of fusogenic liposomes and bacterial membrane vesicles. Overall, this thesis describes the development of both sequential and simultaneous multi-drug delivery microparticle systems for treating antibiotic-resistant bacterial infections, advancing the field of localised and controllable multi-drug delivery.