The effects of individually applied heat or drought stress on cotton’s pollen fertility, and consequently on yield formation, have been extensively studied. In contrast, the effects of their compound stress have received minimal attention. To address this, a pond experiment was conducted using a cotton cultivar, Yuzaomian 9110 and the treatments consisted of control (CK), drought stress (DS), elevated temperature (ET), and the combination of elevated temperature and drought stress (ET+DS). Results revealed that ET+DS resulted in larger decreases in cottonseed number per boll and boll weight than DS or ET, which were attributed to the lower pollen fertility under the combined stress compared to either single stress. The decreases in pollen fertility under all stress conditions were further associated with disturbances in anther carbohydrate and energy metabolism. Pollen viability was negatively correlated with sucrose content, but was positively correlated with starch and ATP contents under different conditions. Specifically, DS increased anther sucrose content by increasing sucrose phosphate synthetase (SPS) activity to enhance sucrose synthesis, and by decreasing sucrose synthetase (SuSy) and acid/alkaline INV activities to restrict sucrose hydrolysis to fructose and glucose. Similar to DS, ET+DS increased anther sucrose content, which was attributed to the restricted sucrose hydrolysis, due to the reduced activities of SuSy and acid/alkaline INV, and acid INV activity even was lower under ET+DS than DS. However, ET enhanced acid invertase (INV) activity to promote sucrose hydrolysis, and down-regulated the expression of GhSUT3A/D (sucrose transporter gene), GhSUT4 (sucrose transporter gene) and GhSWEET55 (encoding Sugars Will Eventually Be Exported Transporters proteins) to inhibit sucrose transport into anthers, so the anther sucrose content was decreased. Furthermore, ET, DS and ET+DS treatments significantly decreased starch synthesis by down-regulating the expression of GhAGP, GhGBSS and GhSSS; however, the ET+DS treatment had a lower GhSSS expression than any single stress, which further inhibited amylopectin synthesis and resulted in lower anther starch content compared to CK and either of the individual stresses. In addition, significant reductions were observed in anther pyruvate content under all stress conditions, which inhibited the ATP production in the tricarboxylic acid cycle. Nevertheless, different pathways were involved in the response of energy metabolism to single and combined stresses. In particular, single ET or DS down-regulated GhHK1 and GhPK to decrease pyruvate formation, while the downregulation of GhHK1 and GhPGK were responsible for the decreased pyruvate content under combined stress. Additionally, either single stress resulted in the upregulation and downregulation of GhATP α subunit and GhATP β subunit of ATP synthase, respectively, the opposite was observed under the condition of combined stress, indicating that differential response mechanisms of ATP synthase are activated between the combined stress and any individual stresses. All these confirmed that elevated temperature combined with drought stress have a unique effect on carbohydrate and energy metabolism of anthers, resulting in larger decreases in pollen fertility, cottonseed number per boll and boll weight than either of the stresses alone.