Despite the cutting-edge research being conducted for the treatment of cancer, it still ranks as the second leading cause of mortality among human beings. Cancer is responsible for 9 million deaths every year, equating to 27,000 deaths per day, which accounts for approximately 18% of the total deaths worldwide. Among men, lung, prostate, colorectal, stomach, and liver cancer are the most prevalent types, whereas breast, colorectal, lung, cervical, and thyroid cancer are the most common among women [[1], [2], [3]]. Dedicated researchers are diligently striving to eradicate cancer worldwide through the development of advanced diagnostic methods and treatment strategies [4]. While advanced diagnostic techniques have greatly facilitated early cancer detection, the challenge of treatment remains daunting. Current treatment strategies lack specificity for cancer cells, often resulting in various side effects and toxicity issues, and some therapies suffer from low patient compliance. The adverse effects of chemotherapy drugs and radiation therapy are closely linked to the unique characteristics of the anticancer agents, which have tendency to accumulate in specific areas of the body, such as the cardiovascular system, brain, kidneys, liver, or lungs, which can lead to complications like heart damage (doxorubicin), neurotoxicity (vincristine) kidney damage (cisplatin), liver damage (methotrexate), or lung scarring (bleomycin) [5]. Additionally, since many anticancer medications target DNA (docetaxel) in rapidly dividing cells, their side effects often affect tissues with high rates of cell division, such as the bone marrow and gastrointestinal tract. This can result in problems like digestive system irritation, decreased bone marrow function, and weakened immune response. Furthermore, chemotherapy drugs and radiation therapy can trigger oxidative stress and inflammation, and are closely associated with genetic instability and the development of secondary tumors [6]. Around 90% of breast cancer patients experienced adverse drug reactions (ADRs), with prevalent ADRs observed in treatment regimens such as fluorouracil, doxorubicin, and cyclophosphamide (85.71%), paclitaxel (91.30%), and docetaxel (90.90%). Similarly, about 83.56% of lung cancer patients faced adverse events, with notable ADRs evident in treatments like pemetrexed+cisplatin (72.22%) causing dysgeusia, anorexia, constipation, neuropathy, and fever, and docetaxel+cisplatin (86.36%) leading to diarrhoea, alopecia, and anorexia [7,8]. Patients facing these side effects may be more prone to non-adherence due to discomfort or distress. Consequently, addressing non-adherence becomes paramount in optimizing treatment outcomes amidst the myriad of challenges posed by ADRs, complex regimens, and other barriers in cancer care [9]. Consequently, there is an urgent need to devise cancer-specific targeting strategies. The targeting of cancer cells can be achieved by delving into both the external and internal microenvironments of these aberrant cells. Cancer cells exhibit distinctive morphological and metabolic properties such as irregular cellular morphology and size, elevated nuclear-cytoplasmic ratio, unchecked cell proliferation, invasive tendencies facilitating metastasis, metabolic shifts favoring heightened glycolysis, resilience against programmed cell death, genetic instability leading to mutation accumulation, evasion of immune detection, and the presence of diverse cellular populations within tumors. That can serve as effective targeting cues. [10]. Cancer cells exhibit an overexpression of negatively charged phosphatidylserine (PS) and phosphatidylethanolamine (PE) on their surface due to an imbalance in the activity of flippase, floppase, and scramblase enzymes induced by oxidative stress. Flippases in normal cells typically retain PS and PE on the inner leaflet of the cell membrane. However, in cancer cells, oxidative stress reduces flippase activity while increasing scramblase activity, leading to the exposure of PS and PE on the outer leaflet of the cell membrane. This imbalance contributes to the negative charge observed on the cell surface [11]. Additionally, the rate of metabolism in cancer cells is very high due to rapid cell division, leading to excessive lactic acid production via the Warburg effect, which further contributes to the negative charge on the cancer cell surface as the produced lactic acid is transported out of cancer cells as lactate anions through HIF-1α-driven MCT4-symporters, leading to a negative charge on the cell surface [12]. Taken together, these features give cancer cells a negative charge, distinguishing them significantly from normal cells [12,13]. Targeting of negatively charged cells can be possible by using positive elements such as positively charged or cationic carriers [14]. In novel drug delivery system use of different carrier system like liposomes, niosomes, ethosomes, microspheres, dendrimers are used. Modifying the surface of these carrier systems by cationic elements could led to the development of charge driven drug delivery system for the targeting of cancer cells [15]. This comprehensive review delves into the intriguing realm of negatively charged cancer cell surfaces, shedding light on diverse targeting strategies, materials, and methodologies involved in the formulation of cationic carrier systems. The exploration extends beyond the fundamental understanding of cancer cell electronegativity to encompass a detailed examination of the myriad types of cationic compounds utilized in these innovative systems. Furthermore, the review illuminates the multifaceted applications of cationic carrier systems, spanning from their pivotal role in protein and peptide delivery to their contributions in imaging techniques, photodynamic therapy, gene delivery, and even their potential as effective antimicrobial agents. This journey unravels the intricate landscape of cationic carrier systems and their transformative potential in cancer therapeutics and beyond.