Drug-targeted delivery has become a top priority in the world of medicine in order to develop more efficient therapeutic agents. This is important as a critical underlying problem in cancer therapy stems from the inability to deliver active therapeutic substances directly to tumor cells without causing collateral damage. In this work, zinc(II) phthalocyanine (ZnPc) was selected as a sensitizer and was linked to different targeting agents, which would be recognized by overexpressed proteins in cancer cells. As targeting agents, we first selected the two ligands (DAA1106, PK11195) of the translocator protein (TSPO) and then Erlotinib a binding group of the ATP domain of tyrosine kinase in epidermal growth factor (EGFR). ZnPc was connected via an ethylene glycol chain to either one (n = 1) or four (n = 4) targeting agents. The biological activity of these conjugates ZnPc(ligand)n was investigated on MDA-MB-231 breast human cancer cells and human hepatoma HepG2 cells, first in the dark (cytotoxicity) and then under irradiation (photodynamic therapy). The dark cytotoxicity was extremely low (IC50 ≥ 50 μM) for all of these compounds, which is a required criterion for further photodynamic application. After irradiation at 650 nm, only the conjugates bearing one targeting ligand such as ZnPc-[DAA1106]1, ZnPc-[PK11195]1, and ZnPc-[Erlo]1 showed photodynamic activity, while those linked to 4 targeting agents were inactive. Importantly, fluorescence imaging microscopy showed the colocalization of ZnPc-[DAA1106]1, ZnPc-[PK11195]1 and ZnPc-[erlo]1, at mitochondria, a result that justifies the observed photodynamic activity of these conjugates. This study first shows the impact of the number and the mode of organization of targeting agents on the ability of the sensitizer to cross the cell membrane. When zinc(II) phthalocyanine carries a single targeting agent, a significant photodynamic activity on MDA-MB-231 breast human cancer cells was measured and localization at the mitochondria was demonstrated by fluorescence imaging, thus proving the potential of the sensitizer linked to a targeting agent to improve selectivity. Another important conclusion from this study for the design of future effective PDT drugs using multivalence effects is to control the arrangement of the targeting agents in order to design molecules that will be able to pass the cell membrane barriers.