This systematic review provides a comprehensive analysis of Alzheimer’s Disease (AD) pathology and its pharmacological advancements. Population aging over last decades render AD becoming more prevalent, indicating a significant sociological and economic burden. Yet, due to the complexity of the brain structure, the researchers must understand AD’s multifactorial pathology and progression mechanisms in order to find an effective treatment. The review will primarily examine the classical amyloid-β hypothesis and tau protein’s involvement, exploring their interplay in neuronal degeneration. Additionally, it also examines the emerging theories of neuroinflammation, prion-like proteins and vascular damages as crucial contributors to AD pathology. Recently, several FDA-approved non-curative drugs have been reported to reduce amyloid-β plaque and/or enhance cognitive function. Consequently, beyond analyzing AD’s pathological hypotheses, critically assessments on recent pharmacological advances using monoclonal antibodies (Aducanumab), cholinesterase inhibitors (Donepezil) and NMDA antagonists (Memantine) are used as examples to compare their clinical efficacies and controversies. Discussion on other factors including ethical considerations, personalized medicine and the transformation of treatment paradigms are included. By identifying a paradigm shift towards a multi-targeted approach which integrates pharmacological and non-pharmacological interventions, this review underscores the necessities of ethical concerns and patient-centred treatments. Thus, this review aims to present an academic consolidation of current knowledge and stimulate further interdisciplinary research, promoting innovation in AD treatment.