Organelles are specialized subunits within cells which carry out vital functions crucial to cellular survival and form a tightly regulated network. Dysfunctions in any of these organelles are linked to numerous diseases impacting virtually every organ system in the human body. Targeted delivery of therapeutics to specific organelles within the cell holds great promise for overcoming challenging diseases and improving treatment outcomes through the minimization of therapeutic dosage and off-target effects. Nanoparticles are versatile and effective tools for therapeutic delivery to specific organelles. Nanoparticles offer several advantageous characteristics, including a high surface area-to-volume ratio for efficient therapeutic loading and the ability to attach targeting moieties (tethers) that enhance delivery. The choice of nanoparticle shape, size, composition, surface properties, and targeting ligands depends on the desired target organelle and therapeutic effect. Various nanoparticle platforms have been explored for organelle targeting, such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. In this review, current and emerging approaches to nanoparticle design are examined in the context of various diseases linked to organelle dysfunction. Specifically, advances in nanoparticle therapies targeting organelles such as the nucleus, mitochondria, lysosomes/endosomes, Golgi apparatus, and endoplasmic reticulum are comprehensively and critically discussed.