Objective assessment of tumor responses and treatment results has been the basis for the advancement of cancer therapies, and imaging plays a key role to provide a "common language" to describe the results of cancer treatment. Although Response Evaluation Criteria in Solid Tumors (RECIST) has been the most widely accepted method for assessing tumor response in the past decades, the limitations of RECIST have increasingly becoming recognized, especially with the recent advances of precision-medicine approaches to cancer. This article reviews the current concept of tumor response evaluations based on RECIST, describes the limitations of RECIST, and proposes strategies to overcome the limitations. The article emphasizes specific limitations in the setting of precision cancer therapy and cancer immunotherapy and discusses the important insights provided by the cutting-edge investigations in the emerging fields.