The receptor tyrosine kinases (RTKs) have been at the forefront of cancer growth and development as well as therapeutic resistance. Targeting RTK has shown promising results in both preclinical and clinical studies. However, the selective targeting of RTK in cancer cells is yet to be achieved to avoid normal cells and systemic toxicity. The small molecule phytochemicals have been shown to modulate the expression as well as activity of many RTKs involved in cancer growth and progression. These phytochemicals alter signaling pathways associated with proliferation, survival, apoptosis, invasion, migration, and metastasis in cancer cells. The natural compounds like curcumin, berberine, fisetin, quercetin, resveratrol, silibinin, and honokiol have exhibited notable anticancer effects in various types of cancer models. These phytochemicals have the potential to overcome drug resistance and improve the effectiveness of treatments, especially tyrosine kinase inhibitors (TKIs), in addition to having chemopreventive benefits by preventing early carcinogenesis. These bioactive natural compounds may be useful as supplemental agents in cancer prevention and also in resolving the shortcomings of existing cancer treatments. Nevertheless, controlled studies are required on natural compounds in clinical settings for their safer utilization in cancer control and management.