Smart nanomaterials with stimuli-responsive imaging enhancement have been widely developed to meet the requirements of accurate cancer diagnosis. However, these imaging nanoenhancers tend to be always on during circulation, which significantly increases the background signal when assessing the imaging performance. To improve unfavorable signal-to-noise ratios, an effective way is to shield the noise signal of these nanoprobes in non-targeted areas. Fortunately, there is a natural mutual shielding effect between some imaging nanomaterials, which provides the possibility of designing engineered nanomaterials with imaging quenching between two different components at the beginning. Once in the tumor microenvironment, the two components will present activated dual-mode imaging ability because of their separation, designated as two-way imaging tuning. This review highlights the design and mechanism of a series of engineered nanomaterials with two-way imaging tuning and their latest applications in the fields of cancer magnetic resonance imaging, fluorescence imaging, and their combination. The challenges and future directions for the improvement of these engineered nanomaterials towards clinical transformation are also discussed. This review aims to introduce the special constraint relationships of imaging components and provide scientists with simpler and more efficient nanoplatform construction ideas, promoting the development of engineered nanomaterials with two-way imaging tuning in cancer theranostics.