The present disclosure relates to a CMOS image sensor having a multiple deep trench isolation (MDTI) structure, and an associated method of formation. In some embodiments, the image sensor comprises a boundary deep trench isolation (BDTI) structure disposed at boundary regions of a pixel region surrounding a photodiode. The BDTI structure has a ring shape from a top view and two columns surrounding the photodiode with the first depth from a cross-sectional view. A multiple deep trench isolation (MDTI) structure is disposed at inner regions of the pixel region overlying the photodiode, the MDTI structure extending from the back-side of the substrate to a second depth within the substrate smaller than the first depth. The MDTI structure has three columns with the second depth between the two columns of the BDTI structure from the cross-sectional view. The MDTI structure is a continuous integral unit having a ring shape.