Over the past decade, machine learning research has made great strides and significant impact in several fields. Its success is greatly attributed to the development of effective machine learning algorithms like deep neural networks (a.k.a. deep learning), availability of large-scale databases and access to specialized hardware like Graphic Processing Units. When designing and training machine learning systems, researchers often assume access to large quantities of data that capture different possible variations. Variations in the data is needed to incorporate desired invariance and robustness properties in the machine learning system, especially in the case of deep learning algorithms. However, it is very difficult to gather such data in a real-world setting. For example, in certain medical/healthcare applications, it is very challenging to have access to data from all possible scenarios or with the necessary amount of variations as required to train the system. Additionally, the over-parameterized and unconstrained nature of deep neural networks can cause them to be poorly trained and in many cases over-confident which, in turn, can hamper their reliability and generalizability. This dissertation is a compendium of my research efforts to address the above challenges. I propose building invariant feature representations by wedding concepts from topological data analysis and Riemannian geometry, that automatically incorporate the desired invariance properties for different computer vision applications. I discuss how deep learning can be used to address some of the common challenges faced when working with topological data analysis methods. I describe alternative learning strategies based on unsupervised learning and transfer learning to address issues like dataset shifts and limited training data. Finally, I discuss my preliminary work on applying simple orthogonal constraints on deep learning feature representations to help develop more reliable and better calibrated models.