Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy.