ABSTRACT Imaging small animal models of cancer has become an essential and integral part of cancer research. The Integrated Small Animal Imaging Research Resource (iSAIRR) has demonstrated its broad usage and applications in advancing research in breast, lung, prostate, ovarian, head and neck, pancreatic, colorectal, and brain cancer. Evolving imaging technologies have also made available different, but complementary, imaging methods for assessing underlying biology and mechanisms, improving diagnosis and detection, and monitoring effects of cancer therapies. To take full advantage of this rapidly changing imaging landscape, and to provide a wider spectrum of imaging capabilities and services, the iSAlRR now offers a broader spectrum of imaging modalities and techniques for in vivo imaging of small animals and ex vivo imaging of tissue/organ specimens with improved operational efficiency and cost effectiveness. The iSAIRR now includes the following Subcores: 1) Magnetic Resonance Imaging and Spectroscopy (MRIS); 2) Optical Imaging (OI); 3) microPET/SPECT/CT imaging, with the image and data analysis components added in this cycle; and 4) Imaging Chemistry. CCSG funds are not requested for the Imaging Chemistry services. The Imaging Chemistry Subcore was established in 2015 using UCCCC Developmental Funds, and brings distinctive capabilities and expertise to our users, including specifically designed contrast agents, and collaborates with the new Cyclotron Facility and developing radiochemistry program enabling unique imaging approaches. During the current funding period, the iSAIRR has been strategically restructured to better support ongoing and future research. Core leadership has been enhanced with new technical directors and an expanded Faculty Oversight Committee representing the changing needs of our users and services of the Core. The Imaging Veterinary Technology Support Subcore was dissolved and a more efficient model has been adopted. Trained veterinary technicians’ effort is distributed across all modalities as needed, with an increased contribution from operators. The 9.4T MRI scanner was recently upgraded, and there are plans to expand the microPET/ SPECT/CT imaging services and capabilities. Going forward, an Ultrasound Imaging Subcore will be established, and available to users with a fee-for-service structure for independent as well as assisted use (no CCSG funds requested). After an internal review and following users’ requests, the image analysis component previously included in the UCCCC Image Computing, Analysis, and Repository Core (ICAR), was incorporated into ISAIRR. More specifically, it has been incorporated into the microPET/SPECT/CT Subcore. Such integration has enhanced the efficiency of this Subcore by providing more organic and inclusive services in molecular imaging.