Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by proteostatic collapse and chronic neuroinflammation, yet the mechanistic crosstalk between autophagy failure and inflammatory signaling remains underexplored in therapeutic frameworks. This chapter addresses this gap by dissecting how amyloid-β plaques and tau tangles disrupt autophagic flux, following NLRP3 inflammasome activation and cytokine-driven inflammation, driving neuronal vulnerability. By elucidating bidirectional pathways such as caspase-1-mediated cleavage of autophagy proteins and autophagy-dependent regulation of inflammasomes, this chapter underscores the necessity of moving beyond singular therapeutic targets toward multimodal strategies. Here, we emphasized molecular mechanisms by integrating preclinical and clinical evidence to bridge cellular biology with translational innovation. Focus has been made on emerging therapeutics to illustrate their synergistic potential in disrupting AD’s self-perpetuating pathology. This chapter balances mechanistic depth with clinical relevance to offer a roadmap for developing combinatory therapies.