Continuous p-dispersion problems with and without boundary constraints are NP-hard optimization problems with numerous real-world applications, notably in facility location and circle packing, which are widely studied in mathematics and operations research. In this work, we concentrate on general cases with a nonconvex multiply connected region that are rarely studied in the literature due to their intractability and the absence of an efficient optimization model. Using the penalty function approach, we design a unified and almost everywhere differentiable optimization model for these complex problems and propose a tabu search–based global optimization (TSGO) algorithm for solving them. Computational results over a variety of benchmark instances show that the proposed model works very well, allowing popular local optimization methods (e.g., the quasi-Newton methods and the conjugate gradient methods) to reach high-precision solutions due to the differentiability of the model. These results further demonstrate that the proposed TSGO algorithm is very efficient and significantly outperforms several popular global optimization algorithms in the literature, improving the best-known solutions for several existing instances in a short computational time. Experimental analyses are conducted to show the influence of several key ingredients of the algorithm on computational performance. History: Accepted by Erwin Pesch, Area Editor for Heuristic Search & Approximation Algorithms. Funding: This work was supported by the National Natural Science Foundation of China [Grants 72122006, 71821001, and 72471100] Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2023.0089 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2023.0089 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .