Malicious Software (malware) attacks across the internet are increasing at an alarming rate. Cyber-attacks have become increasingly more sophisticated and targeted. These targeted attacks are aimed at compromising networks, stealing personal financial information and removing sensitive data or disrupting operations. Current malware detection approaches work well for previously known signatures. However, malware developers utilize techniques to mutate and change software properties (signatures) to avoid and evade detection. Polymorphic malware is practically undetectable with signature-based defensive technologies. Today’s effective detection rate for polymorphic malware detection ranges from 68.75% to 81.25%. New techniques are needed to improve malware detection rates. Improved detection of polymorphic malware can only be accomplished by extracting features beyond the signature realm. Targeted detection for polymorphic malware must rely upon extracting key features and characteristics for advanced analysis. Traditionally, malware researchers have relied on limited dimensional features such as behavior (dynamic) or source/execution code analysis (static). This study’s focus was to extract and evaluate a limited set of multidimensional topological data in order to improve detection for polymorphic malware. This study used multidimensional analysis (file properties, static and dynamic analysis) with machine learning algorithms to improve malware detection. This research demonstrated improved polymorphic malware detection can be achieved with machine learning. This study conducted a number of experiments using a standard experimental testing protocol. This study utilized three advanced algorithms (Metabagging (MB), Instance Based k-Means (IBk) and Deep Learning Multi-Layer Perceptron) with a limited set of multidimensional data. Experimental results delivered detection results above 99.43%. In addition, the experiments delivered near zero false positives. The study’s approach was based on single case experimental design, a well-accepted protocol for progressive testing. The study constructed a prototype to automate feature extraction, assemble files for analysis, and analyze results through multiple clustering algorithms. The study performed an evaluation of large malware sample datasets to understand effectiveness across a wide range of malware. The study developed an integrated framework which automated feature extraction for multidimensional analysis. The feature extraction framework consisted of four modules: 1) a pre-process module that extracts and generates topological features based on static analysis of machine code and file characteristics, 2) a behavioral analysis module that extracts behavioral characteristics based on file execution (dynamic analysis), 3) an input file construction and submission module, and 4) a machine learning module that employs various advanced algorithms. As with most studies, careful attention was paid to false positive and false negative rates which reduce their overall detection accuracy and effectiveness. This study provided a novel approach to expand the malware body of knowledge and improve the detection for polymorphic malware targeting Microsoft operating systems.