Despite the increasing availability of modern treatments, including personalized therapies, there is a strong need to search for new drugs that will be effective in the fight against cancer. The chemotherapeutics currently available to oncologists do not always yield satisfactory outcomes when used in systemic treatments, and patients experience burdensome side effects during their application. In the era of personalized therapies, doctors caring for non-small cell lung cancer (NSCLC) patients have been given a powerful weapon, namely molecularly targeted therapies and immunotherapies. They can be used when genetic variants of the disease qualifying for therapy are diagnosed. These therapies have contributed to the extension of the overall survival time in patients. Nevertheless, effective treatment may be hindered in the case of clonal selection of tumor cells with acquired resistance mutations. The state-of-the-art therapy currently used in NSCLC patients is immunotherapy targeting the immune checkpoints. Although it is effective, some patients have been observed to develop resistance to immunotherapy, but its cause is still unknown. Personalized therapies extend the lifespan and time to cancer progression in patients, but only those with a confirmed marker qualifying for the treatment (gene mutations/rearrangements or PD-L1 expression on tumor cells) can benefit from these therapies. They also cause less burdensome side effects than chemotherapy. The article is focused on compounds that can be used in oncology and produce as few side effects as possible. The search for compounds of natural origin, e.g., plants, bacteria, or fungi, exhibiting anticancer properties seems to be a good solution. This article is a literature review of research on compounds of natural origin that can potentially be used as part of NSCLC therapies.