Colorectal cancer is the third most common cancer worldwide. Despite recent advances in the treatment of this pathology, which include a personalized approach using radio- and chemotherapies in combination with advanced surgical techniques, it is imperative to enhance the performance of these treatments and decrease their detrimental side effects on patients’ health. Nanomedicine is likely the pathway towards solving this challenge by enhancing both the therapeutic and diagnostic capabilities. In particular, plasmonic nanoparticles show remarkable potential due to their dual therapeutic functionalities as photothermal therapy agents and as radiosensitizers in radiotherapy. Their dual functionality, high biocompatibility, easy functionalization, and targeting capabilities make them potential agents for inducing efficient cancer cell death with minimal side effects. This review aims to identify the main challenges in the diagnosis and treatment of colorectal cancer. The heterogeneous nature of this cancer is also discussed from a single-cell point of view. The most relevant works in photo- and radiotherapy using nanotechnology-based therapies for colorectal cancer are addressed, ranging from in vitro studies (2D and 3D cell cultures) to in vivo studies and clinical trials. Although the results using nanoparticles as a photo- and radiosensitizers in photo- and radiotherapy are promising, preliminary studies showed that the possibility of combining both therapies must be explored to improve the treatment efficiency.