It has become necessary to accept the clinical reality of therapeutic agents targeting the cancer-associated immune system. In recent decades, several investigations have highlighted the role of inflammation in cancer development. It has now been recognized that inflammatory cells secrete mediators, including enzymes, chemokines, and cytokines. These secreted substances produce an inflammatory microenvironment that is critically involved in cancer growth. Inflammation may enhance genomic instability leading to DNA damage, activation of oncogenes, or compromised tumor suppressor activity, all of which may promote various phases of carcinogenesis. Conventional cancer treatment includes surgery, radiation, and chemotherapy. However, treatment failure occurs because current strategies are unable to achieve complete local control due to metastasis. Nanoparticles (NPs) are a broad spectrum of drug carriers typically below the size of 100 nm, targeting tumor sites while reducing off-target consequences. More importantly, NPs can stimulate innate and adaptive immune systems in the tumor microenvironment (TME); hence, they induce a cancer-fighting immune response. Strikingly, targeting cancer cells with NPs helps eliminate drug resistance and tumor recurrence, as well as prevents inflammation. Throughout this review, we provide recent data on the role of inflammation in cancer and explore nano-therapeutic initiatives to target significant mediators, for example, nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins (ILs) associated with cancer-related inflammation, to escort the immunomodulators to cancer cells and associated systemic compartments. We also highlight the necessity of better identifying inflammatory pathways in cancer pathophysiology to develop effective treatment plans.