Developing small molecules that inherently integrate highly tumor-targeted near-infrared fluorescence (NIRF) imaging with potent therapeutic effects remains challenging in anticancer theranostics. Here, we synthesized and characterized a series of heptamethine cyanine PSs with symmetric and asymmetric structures. Among them, we first discovered that asymmetric structures significantly enhanced tumor targeting. Also, a novel mitochondria-targeted asymmetric compound 17 exhibited superior NIRF imaging capability, exceptional tumor selectivity (TNR = 8.54), and strong antitumor activity. Compound 17 selectively accumulates in mitochondria, driven by MMP, where it generates ROS, induces DNA damage, and triggers senescence, apoptosis, and necrosis. Its strong therapeutic efficacy was demonstrated across multiple models, including patient-derived xenograft (PDX), where it allowed precise tumor visualization, significantly suppressed tumor growth with a single administration, and showed no detectable toxicity. Notably, the single-dye small molecule 17 was retained in tumors for over 120 h, enabling prolonged imaging, targeted therapy, and drug delivery for integrated antitumor treatment.