Bispecific antibodies (bsAbs) are a promising class of therapeutic molecules that can simultaneously target two different antigens, offering synergistic effects beyond conventional monoclonal antibodies. Despite their therapeutic potential, designing and constructing bsAbs is challenging due to increased structural complexity, leading to issues such as reduced stability and impurities. This review highlights key design considerations and state-of-the-art engineering principles for developing high-quality bsAbs with desired functions and favorable drug-like properties. BsAbs can act through various mechanisms, including in-trans and in-cis binding, which enable different therapeutic effects. In-trans binding creates physical links between cells, while in-cis binding activates or blocks receptor signaling. The design of bsAbs requires careful consideration of molecular geometry, chain pairing, and the relative orientation of antigen-binding domains to ensure optimal function and stability. Common bsAb formats include symmetric and asymmetric designs, each with distinct advantages. Symmetric bsAbs, such as scFv-IgG fusions, are easier to produce and have fewer impurities, while asymmetric bsAbs offer greater flexibility in valency and can mimic native IgG structures. Chain steering strategies, such as the knob-into-hole (KiH) method, are used to ensure proper pairing of antibody chains and reduce impurities. The molecular geometry of bsAbs significantly influences their potency and functionality. Proper design of interparatopic spacing and binding affinities is crucial for effective target engagement. Additionally, developability considerations, such as expression levels, stability, and solubility, are essential for successful therapeutic development. This review emphasizes the importance of strategic design and engineering to harness the full therapeutic potential of bsAbs, while addressing challenges related to their structural complexity and practical implementation. The insights provided offer a roadmap for future research and development of improved bispecific antibody therapeutics.Bispecific antibodies (bsAbs) are a promising class of therapeutic molecules that can simultaneously target two different antigens, offering synergistic effects beyond conventional monoclonal antibodies. Despite their therapeutic potential, designing and constructing bsAbs is challenging due to increased structural complexity, leading to issues such as reduced stability and impurities. This review highlights key design considerations and state-of-the-art engineering principles for developing high-quality bsAbs with desired functions and favorable drug-like properties. BsAbs can act through various mechanisms, including in-trans and in-cis binding, which enable different therapeutic effects. In-trans binding creates physical links between cells, while in-cis binding activates or blocks receptor signaling. The design of bsAbs requires careful consideration of molecular geometry, chain pairing, and the relative orientation of antigen-binding domains to ensure optimal function and stability. Common bsAb formats include symmetric and asymmetric designs, each with distinct advantages. Symmetric bsAbs, such as scFv-IgG fusions, are easier to produce and have fewer impurities, while asymmetric bsAbs offer greater flexibility in valency and can mimic native IgG structures. Chain steering strategies, such as the knob-into-hole (KiH) method, are used to ensure proper pairing of antibody chains and reduce impurities. The molecular geometry of bsAbs significantly influences their potency and functionality. Proper design of interparatopic spacing and binding affinities is crucial for effective target engagement. Additionally, developability considerations, such as expression levels, stability, and solubility, are essential for successful therapeutic development. This review emphasizes the importance of strategic design and engineering to harness the full therapeutic potential of bsAbs, while addressing challenges related to their structural complexity and practical implementation. The insights provided offer a roadmap for future research and development of improved bispecific antibody therapeutics.