Alzheimer’s disease (AD) remains one of the most pressing medical challenges, with limited therapeutic options and heterogeneous disease trajectories complicating diagnosis and treatment. Recent advances in computational biology and artificial intelligence (AI) together with availability of rich molecular and clinical data, offer new opportunities to address these challenges by integrating molecular, clinical, and systems-level insights. In our recent studies, we developed a cell-type-directed, network-correcting approach to identify and prioritize rational drug combinations for AD, enabling targeted modulation of disease-relevant pathways across distinct cellular contexts (Li et al., Cell 2025). Complementarily, by leveraging large-scale electronic medical records (EMRs) integrated with biological knowledge networks, we demonstrated the ability to predict disease onset and progression while uncovering mechanistic insights into AD heterogeneity (Tang et al., Nature Aging 2024). Together, these complementary approaches illustrate the power of combining real-world clinical data, knowledge networks, and systems pharmacology to advance precision medicine for AD. This work highlights a paradigm shift toward AI-enabled, data-driven strategies that bridge molecular discovery and clinical application, ultimately informing novel therapeutic interventions and improving patient care.