Breast cancer is one of the leading causes of cancer-related mortality in women worldwide, highlighting the importance of effective therapies. This study evaluates the interaction between camptothecin, a potent anticancer agent, and two key receptors implicated in breast cancer progression: HER2 (human epidermal growth factor receptor 2) and EGFR (epidermal growth factor receptor), using molecular docking. The results reveal a stronger binding affinity between camptothecin and HER2 than EGFR, in contrast to neratinib, which demonstrated affinity exclusively for HER2. Camptothecin exhibits significant hydrophobic and pi-alkyl interactions with HER2, whereas its interactions with EGFR are primarily mediated by hydrogen bonds. Molecular dynamics (MD) simulations of the camptothecin-HER2 complex indicate stable binding, with minimal fluctuations observed over 100 nanoseconds, confirming the stability of the ligand–receptor interaction. Pharmacokinetic evaluations, based on Lipinski’s rule of five, demonstrate that camptothecin adheres to essential drug-likeness parameters, suggesting favorable bioavailability. Furthermore, the analysis comparing the pharmacological properties of camptothecin with other well-known anticancer compounds, such as neratinib, shows that camptothecin exhibited superior compliance with drug-likeness rules. Despite its low solubility, the binding stability and pharmacokinetic profile suggest its potential as an effective therapeutic agent for breast cancer, particularly when combined with drug delivery systems that enhance solubility. This work underscores the importance of receptor-specific ligand interactions in drug design and highlights the need for further studies into camptothecin’s clinical applications, especially in HER2-positive breast cancer treatment.