Parkinson’s disease (PD) is a complex neurodegenerative disorder driven by the loss of dopamine-producing neurons in the substantia nigra and a convergence of cellular dysfunctions, including α-synuclein accumulation, mitochondrial and lysosomal failure, and chronic inflammation. This chapter explains PD as a systems-level disorder. In PD, disrupted protein clearance through chaperone-mediated autophagy (CMA), impaired mitochondrial quality control, and overactive immune responses form a self-reinforcing cycle of damage. Modified α-synuclein blocks CMA by overloading LAMP2A, leading to protein build-up and lysosomal stress, while mitochondrial defects, caused by abnormal fission–fusion dynamics and impaired mitophagy, lead to excess reactive oxygen species (ROS). Oxidative by-products from dopamine metabolism and lipid breakdown place additional strain on mitochondria, impairing the function of key components like Parkin and complex I. As cellular damage progresses, mitochondrial fragments and reactive oxygen species (ROS) act as distress signals, triggering toll-like receptor pathways and initiating inflammatory responses through glial cells. This inflammation, in turn, disrupts synaptic communication and contributes to neuronal vulnerability. In response, emerging treatments are being developed to address these underlying cellular disturbances, such as compounds that enhance autophagy, drugs that restore lysosomal function, targeted immune therapies, and advanced delivery systems using CRISPR technology. This chapter underscores the importance of tailoring these interventions to the diverse genetic backgrounds of PD patients and recommends future research into spatial gene expression and organelle coordination as pathways toward more effective, individualized therapies.