We investigate the generalization boundaries of current Multimodal Large Language Models (MLLMs) via comprehensive evaluation under out-of-distribution scenarios and domain-specific tasks. We evaluate their zero-shot generalization across synthetic images, real-world distributional shifts, and specialized datasets like medical and molecular imagery. Empirical results indicate that MLLMs struggle with generalization beyond common training domains, limiting their direct application without adaptation. To understand the cause of unreliable performance, we analyze three hypotheses: semantic misinterpretation, visual feature extraction insufficiency, and mapping deficiency. Results identify mapping deficiency as the primary hurdle. To address this problem, we show that in-context learning (ICL) can significantly enhance MLLMs' generalization, opening new avenues for overcoming generalization barriers. We further explore the robustness of ICL under distribution shifts and show its vulnerability to domain shifts, label shifts, and spurious correlation shifts between in-context examples and test data.