In this concept, we present a comprehensive study on the development and application of COX‐2‐specific fluorescent probes for cancer imaging and diagnosis. Targetting cancer cells and measuring cancer‐related activities in specific organelles quickly and accurately are crucial factors for early diagnosis and research on cancer pathology and treatment. This concept explores a variety of probes which include BDIMC1‐2, TPI‐IMC, YZP1, IQ‐1, ANQ‐IMC‐6, Niblue‐C6‐IMC, AZB‐IMC2, CMP, CF3‐Fluorocoxib, IBPC1, CoxFluor, etc. and each one demonstrates unique mechanisms and high selectivity towards COX‐2 enzymes. These probes were designed to enhance fluorescence upon binding to COX‐2 which enable precise visualization of tumor and inflamed tissues. The research emphasizes the importance of COX‐2 as a biomarker in cancer diagnostics, particularly in identifying cancer stem cells and inflamed tissues. This concept highlights the potentiality of these probes in non‐invasive imaging techniques which offering significant advancements in cancer diagnosis and monitoring. The in vivo and in vitro experiments, including applications in mouse models and human tissue samples, confirm the efficacy of these probes in providing detailed imaging for clinical and research applications.